Грелиновые механизмы пищевого вознаграждения. Часть 1. Грелин и дофамин

Обложка

Цитировать

Полный текст

Открытый доступ Открытый доступ
Доступ закрыт Доступ предоставлен
Доступ закрыт Только для подписчиков

Аннотация

Пищевое поведение включает как удовлетворение метаболических потребностей в питательных веществах, так и гедонические аспекты, связанные с получением удовольствия от приема пищи. Орексигенный гормон грелин повышает мотивацию к потреблению пищи. Ключевую роль в механизмах вознаграждения играет дофаминергическая мезолимбическая система. Грелин регулирует активность этой системы, действуя на нескольких уровнях структурной организации мозга. Кроме того, модулируя систему награды, грелин усиливает подкрепляющие свойства непищевых стимулов. Рассматривается иерархия грелин-чувствительных нейросетей, а также афферентные связи и реципроктные взаимодействия между ее компонентами, опосредующие действие грелина на процесс мотивации в метаболическом и гедоническом питании.

Об авторах

Борис Андреевич Рейхардт

Институт экспериментальной медицины

Автор, ответственный за переписку.
Email: reihardt@mail.ru
ORCID iD: 0000-0003-3371-9161
SPIN-код: 8980-1073

канд. мед. наук, старший научный сотрудник

Россия, Санкт-Петербург

Петр Дмитриевич Шабанов

Институт экспериментальной медицины

Email: pdshabanov@mail.ru
ORCID iD: 0000-0003-1464-1127
SPIN-код: 8974-7477

д-р мед. наук, профессор, заведующий отделом

Россия, Санкт-Петербург

Список литературы

  1. Kojima M, Kangawa K. Structure and function of ghrelin. Results Probl Cell Differ. 2008;46:89–115. doi: 10.1007/400_2007_049
  2. Delporte C. Structure and physiological actions of ghrelin. Scientifica (Cairo). 2013;2013:518909. doi: 10.1155/2013/518909
  3. Müller TD, Nogueiras R, Andermann ML, et al. Ghrelin. Mol Metab. 2015;4(6):437–460. doi: 10.1016/j.molmet.2015.03.005
  4. Al Massadi O, Nogueiras R, Dieguez C, et al. Ghrelin and food reward. Neuropharmacology. 2019;148:131–138. doi: 10.1016/j.neuropharm.2019.01.001.
  5. Shabanov PD, Lebedev AA, Bychkov ER, et al. Neurochemical mechanisms and pharmacology of ghrelins. Reviews on Clinical Pharmacology and Drug Therapy. 2020;18(1):5–22. (In Russ.) doi: 10.17816/RCF1815-22
  6. Hougland JL. Ghrelin octanoylation by ghrelin O-acyltransferase: Unique protein biochemistry underlying metabolic signaling. Biochem Soc Trans. 2019;47(1):169–178. doi: 10.1042/BST20180436
  7. Castañeda TR, Tong J, Datta R, et al. Ghrelin in the regulation of body weight and metabolism. Front Neuroendocrinol. 2010;31(1): 44–60. doi: 10.1016/j.yfrne.2009.10.008
  8. Albarrán-Zeckler RG, Smith RG. The ghrelin receptors (GHS-R1a and GHS-R1b). Endocr Dev. 2013;25:5–15. doi: 10.1159/000346042
  9. Yin Y, Li Y, Zhang W. The growth hormone secretagogue receptor: its intracellular signaling and regulation. Int J Mol Sci. 2014;15(3):4837–4855. doi: 10.3390/ijms15034837
  10. Zigman JM, Jones JE, Lee CE, et al. Expression of ghrelin receptor mRNA in the rat and the mouse brain. J Comp Neurol. 2006;494(3):528–548. doi: 10.1002/cne.20823
  11. Els S, Beck-Sickinger AG, Chollet C. Ghrelin receptor: high constitutive activity and methods for developing inverse agonists. Methods Enzymol. 2010;485:103–121. doi: 10.1016/B978-0-12-381296-4.00006-3
  12. Banks WA, Burney BO, Robinson SM. Effects of triglycerides, obesity, and starvation on ghrelin transport across the blood-brain barrier. Peptides. 2008;29(11):2061–2065. doi: 10.1016/j.peptides.2008.07.001
  13. Banks WA, Tschöp M, Robinson SM, et al. Extent and direction of ghrelin transport across the blood-brain barrier is determined by its unique primary structure. J Pharmacol Exp Ther. 2002;302(2): 822–827. doi: 10.1124/jpet.102.034827
  14. Cowley MA, Smith RG, Diano S, et al. The distribution and mechanism of action of ghrelin in the CNS demonstrates a novel hypothalamic circuit regulating energy homeostasis. Neuron. 2003;37(4):649–661. doi: 10.1016/s0896-6273(03)00063-1
  15. Sternson SM, Eiselt AK. Three Pillars for the Neural Control of Appetite. Annu Rev Physiol. 2017;79:401–423. doi: 10.1146/annurev-physiol-021115-104948
  16. Yanagi S, Sato T, Kangawa K, et al. The Homeostatic Force of Ghrelin. Cell Metab. 2018;27(4):786–804. doi: 10.1016/j.cmet.2018.02.008
  17. Serrenho D, Santos SD, Carvalho AL. The Role of Ghrelin in Regulating Synaptic Function and Plasticity of Feeding-Associated Circuits. Front Cell Neurosci. 2019;13:205. doi: 10.3389/fncel.2019.00205
  18. Sun Y, Wang P, Zheng H, et al. Ghrelin stimulation of growth hormone release and appetite is mediated through the growth hormone secretagogue receptor. Proc Natl Acad Sci USA. 2004;101(13): 4679–4684. doi: 10.1073/pnas.0305930101
  19. Hsu TM, Suarez AN, Kanoski SE. Ghrelin: A link between memory and ingestive behavior. Physiol Behav. 2016;162:10–17. doi: 10.1016/j.physbeh.2016.03.039
  20. Farokhnia M, Faulkner ML, Piacentino D, et al. Ghrelin: From a gut hormone to a potential therapeutic target for alcohol use disorder. Physiol Behav. 2019;204:49–57. doi: 10.1016/j.physbeh.2019.02.008
  21. Volkow ND, Wise RA, Baler R. The dopamine motive system: implications for drug and food addiction. Nat Rev Neurosci. 2017;18(12):741–752. doi: 10.1038/nrn.2017.130
  22. Wise RA. Dopamine, learning and motivation. Nat Rev Neurosci. 2004;5(6):483–494. doi: 10.1038/nrn1406
  23. Abizaid A. Ghrelin and dopamine: new insights on the peripheral regulation of appetite. J Neuroendocrinol. 2009;21(9): 787–793. doi: 10.1111/j.1365–2826.2009.01896.x
  24. Dickson SL, Egecioglu E, Landgren S, et al. The role of the central ghrelin system in reward from food and chemical drugs. Mol Cell Endocrinol. 2011;340(1):80–87. doi: 10.1016/j.mce.2011.02.017
  25. Perello M, Dickson SL. Ghrelin signalling on food reward: a salient link between the gut and the mesolimbic system. J Neuroendocrinol. 2015;27(6):424–434. doi: 10.1111/jne.12236
  26. Klawonn AM, Malenka RC. Nucleus Accumbens Modulation in Reward and Aversion. Cold Spring Harb Symp Quant Biol. 2018;83:119–129. doi: 10.1101/sqb.2018.83.037457
  27. Maiorov VI. The functions of dopamine in operant conditioned reflexes. Neurosci Behav Physi. 2019;49:887–893. doi: 10.1007/s11055-019-00815-y
  28. Hernandez L, Hoebel BG. Food reward and cocaine increase extracellular dopamine in the nucleus accumbens as measured by microdialysis. Life Sci. 1988;42(18):1705–1712. doi: 10.1016/0024-3205(88)90036-7
  29. Day JJ, Roitman MF, Wightman RM, et al. Associative learning mediates dynamic shifts in dopamine signaling in the nucleus accumbens. Nat Neurosci. 2007;10(8):1020–1028. doi: 10.1038/nn1923
  30. Hart AS, Clark JJ, Phillips PEM. Dynamic shaping of dopamine signals during probabilistic Pavlovian conditioning. Neurobiol Learn Mem. 2015;117:84–92. doi: 10.1016/j.nlm.2014.07.010
  31. Palmiter RD. Is dopamine a physiologically relevant mediator of feeding behavior? Trends Neurosci. 2007;30(8):375–381. doi: 10.1016/j.tins.2007.06.004
  32. Sheveleva MV, Lebedev AA, Roik RO, et al. Neurobiological mechanisms of the rewars and punishment systems in the brain afteractivation of nucleus accumbens. Reviews on Clinical Pharmacology and Drug Therapy 2013;11(3):3–19.
  33. Ranaldi R. Dopamine and reward seeking: the role of ventral tegmental area. Rev Neurosci. 2014;25(5):621–630. doi: 10.1515/revneuro-2014-0019
  34. Hsu TM, McCutcheon JE, Roitman MF. Parallels and Overlap: The Integration of Homeostatic Signals by Mesolimbic Dopamine Neurons. Front Psychiatry. 2018;9:410. doi: 10.3389/fpsyt.2018.00410
  35. Schultz W. Recent advances in understanding the role of phasic dopamine activity [version 1; peer review: 3 approved]. F1000Research 2019;8(F1000 Faculty Rev):1680. doi: 10.12688/f1000research.19793.1
  36. Salamone JD, Pardo M, Yohn SE, et al. Mesolimbic Dopamine and the Regulation of Motivated Behavior. Curr Top Behav Neurosci. 2016;27:231–257. doi: 10.1007/7854_2015_383
  37. Björklund A, Dunnett SB. Dopamine neuron systems in the brain: an update. Trends Neurosci. 2007;30(5):194–202. doi: 10.1016/j.tins.2007.03.006
  38. Perelló M, Zigman JM. The role of ghrelin in reward-based eating. Biol Psychiatry. 2012;72(5):347–353. doi: 10.1016/j.biopsych.2012.02.016
  39. Wren AM, Small CJ, Ward HL, et al. The novel hypothalamic peptide ghrelin stimulates food intake and growth hormone secretion. Endocrinology. 2000;141(11):4325–4328. doi: 10.1210/endo.141.11.7873
  40. Abizaid A, Horvath TL. Ghrelin and the central regulation of feeding and energy balance. Indian J Endocrinol Metab. 2012;16(Suppl 3): S617–S626. doi: 10.4103/2230-8210.105580
  41. Novelle MG, Diéguez C. Food Addiction and Binge Eating: Lessons Learned from Animal Models. Nutrients. 2018;10(1):71. doi: 10.3390/nu10010071
  42. Shimbara T, Mondal MS, Kawagoe T, et al. Central administration of ghrelin preferentially enhances fat ingestion. Neurosci Lett. 2004;369(1):75–79. doi: 10.1016/j.neulet.2004.07.060
  43. Disse E, Bussier AL, Veyrat-Durebex C, et al. Peripheral ghrelin enhances sweet taste food consumption and preference, regardless of its caloric content. Physiol Behav. 2010;101(2):277–281. doi: 10.1016/j.physbeh.2010.05.017
  44. Keen-Rhinehart E, Bartness TJ. Peripheral ghrelin injections stimulate food intake, foraging, and food hoarding in Siberian hamsters. Am J Physiol Regul Integr Comp Physiol. 2005;288(3): R716–R722. doi: 10.1152/ajpregu.00705.2004
  45. Perello M, Sakata I, Birnbaum S, et al. Ghrelin increases the rewarding value of high-fat diet in an orexin-dependent manner. Biol Psychiatry. 2010;67(9):880–886. doi: 10.1016/j.biopsych.2009.10.030
  46. Weinberg ZY, Nicholson ML, Currie PJ. 6-Hydroxydopamine lesions of the ventral tegmental area suppress ghrelin’s ability to elicit food-reinforced behavior. Neurosci Lett. 2011;499(2):70–73. doi: 10.1016/j.neulet.2011.05.034
  47. Finger BC, Dinan TG, Cryan JF. Diet-induced obesity blunts the behavioural effects of ghrelin: studies in a mouse-progressive ratio task. Psychopharmacology (Berl). 2012;220(1):173–181. doi: 10.1007/s00213-011-2468-0
  48. Skibicka KP, Hansson C, Egecioglu E, et al. Role of ghrelin in food reward: impact of ghrelin on sucrose self-administration and mesolimbic dopamine and acetylcholine receptor gene expression. Addict Biol. 2012;17(1):95–107. doi: 10.1111/j.1369-1600.2010.00294.x
  49. Skibicka KP, Hansson C, Alvarez-Crespo M, et al. Ghrelin directly targets the ventral tegmental area to increase food motivation. Neuroscience. 2011;180:129–137. doi: 10.1016/j.neuroscience.2011.02.016
  50. Jerlhag E. Systemic administration of ghrelin induces conditioned place preference and stimulates accumbal dopamine. Addict Biol. 2008;13(3–4):358–363. doi: 10.1111/j.1369-1600.2008.00125.x
  51. Lockie SH, Dinan T, Lawrence AJ, et al. Diet-induced obesity causes ghrelin resistance in reward processing tasks. Psychoneuroendocrinology. 2015;62:114–120. doi: 10.1016/j.psyneuen.2015.08.004
  52. Egecioglu E, Jerlhag E, Salomé N, et al. Ghrelin increases intake of rewarding food in rodents. Addict Biol. 2010;15(3):304–311. doi: 10.1111/j.1369-1600.2010.00216.x
  53. Zallar LJ, Farokhnia M, Tunstall BJ, et al. The Role of the Ghrelin System in Drug Addiction. Int Rev Neurobiol. 2017;136:89–119. doi: 10.1016/bs.irn.2017.08.002
  54. Jerlhag E. Gut-brain axis and addictive disorders: A review with focus on alcohol and drugs of abuse. Pharmacol Ther. 2019;196: 1–14. doi: 10.1016/j.pharmthera.2018.11.005.
  55. Schéle E, Pfabigan DM, Simrén J, et al. Ghrelin Induces Place Preference for Social Interaction in the Larger Peer of a Male Rat Pair. Neuroscience. 2020;447:148–154. doi: 10.1016/j.neuroscience.2020.01.027
  56. Egecioglu E, Prieto-Garcia L, Studer E, et al. The role of ghrelin signalling for sexual behaviour in male mice. Addict Biol. 2016;21(2):348–359. doi: 10.1111/adb.12202
  57. Prieto-Garcia L, Egecioglu E, Studer E, et al. Ghrelin and GHS-R1A signaling within the ventral and laterodorsal tegmental area regulate sexual behavior in sexually naïve male mice. Psychoneuroendocrinology. 2015;62:392–402. doi: 10.1016/j.psyneuen.2015.09.009
  58. Jerlhag E, Engel JA. Ghrelin receptor antagonism attenuates nicotine-induced locomotor stimulation, accumbal dopamine release and conditioned place preference in mice. Drug Alcohol Depend. 2011;117(2–3):126–131. doi: 10.1016/j.drugalcdep.2011.01.010
  59. Jerlhag E, Egecioglu E, Landgren S, et al. Requirement of central ghrelin signaling for alcohol reward. Proc Natl Acad Sci USA. 2009;106(27):11318–11323. doi: 10.1073/pnas.0812809106
  60. Davis KW, Wellman PJ, Clifford PS. Augmented cocaine conditioned place preference in rats pretreated with systemic ghrelin. Regul Pept. 2007;140(3):148–152. doi: 10.1016/j.regpep.2006.12.003
  61. Schuette LM, Gray CC, Currie PJ. Microinjection of Ghrelin into the Ventral Tegmental Area Potentiates Cocaine-Induced Conditioned Place Preference. J Behav Brain Sci. 2013;3(8):276–580. doi: 10.4236/jbbs.2013.38060
  62. Engel JA, Nylander I, Jerlhag E. A ghrelin receptor (GHS-R1A) antagonist attenuates the rewarding properties of morphine and increases opioid peptide levels in reward areas in mice. Eur Neuropsychopharmacol. 2015;25(12):2364–2371. doi: 10.1016/j.euroneuro.2015.10.004
  63. Sustkova-Fiserova M, Jerabek P, Havlickova T, et al. Ghrelin and endocannabinoids participation in morphine-induced effects in the rat nucleus accumbens. Psychopharmacology (Berl). 2016;233(3): 469–484. doi: 10.1007/s00213-015-4119-3
  64. Jerabek P, Havlickova T, Puskina N, et al. Ghrelin receptor antagonism of morphine-induced conditioned place preference and behavioral and accumbens dopaminergic sensitization in rats. Neurochem Int. 2017;110:101–113. doi: 10.1016/j.neuint.2017.09.013
  65. Fulton S, Woodside B, Shizgal P. Modulation of brain reward circuitry by leptin. Science. 2000;287(5450):125–128. doi: 10.1126/science.287.5450.125
  66. Wellman PJ, Clifford PS, Rodriguez JA. Ghrelin and ghrelin receptor modulation of psychostimulant action. Front Neurosci. 2013;7:171. doi: 10.3389/fnins.2013.00171
  67. Piazza PV, Le Moal M. Glucocorticoids as a biological substrate of reward: physiological and pathophysiological implications. Brain Res Brain Res Rev. 1997;25(3):359–372. doi: 10.1016/s0165-0173(97)00025-8
  68. Jerlhag E, Egecioglu E, Dickson SL, et al. Ghrelin stimulates locomotor activity and accumbal dopamine-overflow via central cholinergic systems in mice: implications for its involvement in brain reward. Addict Biol. 2006;11(1):45–54. doi: 10.1111/j.1369-1600.2006.00002.x
  69. Jerlhag E, Egecioglu E, Dickson SL, et al. Ghrelin administration into tegmental areas stimulates locomotor activity and increases extracellular concentration of dopamine in the nucleus accumbens. Addict Biol. 2007;12(1):6–16. doi: 10.1111/j.1369-1600.2006.00041.x
  70. Jerlhag E, Egecioglu E, Dickson SL, et al. Alpha-conotoxin MII-sensitive nicotinic acetylcholine receptors are involved in mediating the ghrelin-induced locomotor stimulation and dopamine overflow in nucleus accumbens. Eur Neuropsychopharmacol. 2008;18(7): 508–518. doi: 10.1016/j.euroneuro.2008.02.006
  71. McCallum SE, Taraschenko OD, Hathaway ER, et al. Effects of 18-methoxycoronaridine on ghrelin-induced increases in sucrose intake and accumbal dopamine overflow in female rats. Psychopharmacology (Berl). 2011;215(2):247–256. doi: 10.1007/s00213-010-2132-0
  72. Quarta D, Di Francesco C, Melotto S, et al. Systemic administration of ghrelin increases extracellular dopamine in the shell but not the core subdivision of the nucleus accumbens. Neurochem Int. 2009;54(2):89–94. doi: 10.1016/j.neuint.2008.12.006
  73. Pfaus JG, Damsma G, Wenkstern D, et al. Sexual activity increases dopamine transmission in the nucleus accumbens and striatum of female rats. Brain Res. 1995;693(1–2):21–30. doi: 10.1016/0006-8993(95)00679-k
  74. Cone JJ, Roitman JD, Roitman MF. Ghrelin regulates phasic dopamine and nucleus accumbens signaling evoked by food-predictive stimuli. J Neurochem. 2015;133(6):844–856. doi: 10.1111/jnc.13080
  75. Sombers LA, Beyene M, Carelli RM, et al. Synaptic overflow of dopamine in the nucleus accumbens arises from neuronal activity in the ventral tegmental area. J Neurosci. 2009;29(6):1735–1742. doi: 10.1523/JNEUROSCI.5562-08.2009
  76. Surmeier DJ, Ding J, Day M, et al. D1 and D2 dopamine-receptor modulation of striatal glutamatergic signaling in striatal medium spiny neurons. Trends Neurosci. 2007;30(5):228–235. doi: 10.1016/j.tins.2007.03.008
  77. Morales M, Margolis EB. Ventral tegmental area: cellular heterogeneity, connectivity and behaviour. Nat Rev Neurosci. 2017;18(2): 73–85. doi: 10.1038/nrn.2016.165
  78. Yang H, de Jong JW, Tak Y, et al. Nucleus Accumbens Subnuclei Regulate Motivated Behavior via Direct Inhibition and Disinhibition of VTA Dopamine Subpopulations. Neuron. 2018;97(2):434–449.e4. doi: 10.1016/j.neuron.2017.12.022
  79. Branch SY, Goertz RB, Sharpe AL, et al. Food restriction increases glutamate receptor-mediated burst firing of dopamine neurons. J Neurosci. 2013;33(34):13861–13872. doi: 10.1523/JNEUROSCI.5099-12.2013
  80. Van der Plasse G, van Zessen R, Luijendijk MC, et al. Modulation of cue-induced firing of ventral tegmental area dopamine neurons by leptin and ghrelin. Int J Obes (Lond). 2015;39(12):1742–1749. doi: 10.1038/ijo.2015.131
  81. Hung LW, Neuner S, Polepalli JS, et al. Gating of social reward by oxytocin in the ventral tegmental area. Science. 2017;357(6358): 1406–1411. doi: 10.1126/science.aan4994
  82. Morikawa H, Morrisett RA. Ethanol action on dopaminergic neurons in the ventral tegmental area: interaction with intrinsic ion channels and neurotransmitter inputs. Int Rev Neurobiol. 2010;91: 235–288. doi: 10.1016/S0074-7742(10)91008-8
  83. Koulchitsky S, De Backer B, Quertemont E, et al. Differential effects of cocaine on dopamine neuron firing in awake and anesthetized rats. Neuropsychopharmacology. 2012;37(7):1559–1571. doi: 10.1038/npp.2011.339
  84. Creed M, Kaufling J, Fois GR, et al. Cocaine Exposure Enhances the Activity of Ventral Tegmental Area Dopamine Neurons via Calcium-Impermeable NMDARs. J Neurosci. 2016;36(42):10759–10768. doi: 10.1523/JNEUROSCI.1703-16.2016
  85. Juarez B, Han MH. Diversity of Dopaminergic Neural Circuits in Response to Drug Exposure. Neuropsychopharmacology. 2016;41(10):2424–2446. doi: 10.1038/npp.2016.32
  86. Abizaid A, Liu ZW, Andrews ZB, et al. Ghrelin modulates the activity and synaptic input organization of midbrain dopamine neurons while promoting appetite. J Clin Invest. 2006;116(12):3229–3239. doi: 10.1172/JCI29867
  87. Guan XM, Yu H, Palyha OC, et al. Distribution of mRNA encoding the growth hormone secretagogue receptor in brain and peripheral tissues. Brain Res Mol Brain Res. 1997;48(1):23–29. doi: 10.1016/s0169-328x(97)00071-5
  88. Jerlhag E, Egecioglu E, Dickson SL, et al. Glutamatergic regulation of ghrelin-induced activation of the mesolimbic dopamine system. Addict Biol. 2011;16(1):82–91. doi: 10.1111/j.1369-1600.2010.00231.x
  89. Falk S, Lund C, Clemmensen C. Muscarinic receptors in energy homeostasis: Physiology and pharmacology. Basic Clin Pharmacol Toxicol. 2020;126(Suppl 6):66–76. doi: 10.1111/bcpt.13311
  90. Xiao C, Zhou CY, Jiang JH, et al. Neural circuits and nicotinic acetylcholine receptors mediate the cholinergic regulation of midbrain dopaminergic neurons and nicotine dependence. Acta Pharmacol Sin. 2020;41(1):1–9. doi: 10.1038/s41401-019-0299-4
  91. Picciotto MR, Higley MJ, Mineur YS. Acetylcholine as a neuromodulator: cholinergic signaling shapes nervous system function and behavior. Neuron. 2012;76(1):116–129. doi: 10.1016/j.neuron.2012.08.036
  92. Eglen RM. Muscarinic receptor subtypes in neuronal and non-neuronal cholinergic function. Auton Autacoid Pharmacol. 2006;26(3):219–233. doi: 10.1111/j.1474-8673.2006.00368.x
  93. Lebois EP, Thorn C, Edgerton JR, et al. Muscarinic receptor subtype distribution in the central nervous system and relevance to aging and Alzheimer’s disease. Neuropharmacology. 2018;136(Pt C): 362–373. doi: 10.1016/j.neuropharm.2017.11.018
  94. Gronier B, Rasmussen K. Activation of midbrain presumed dopaminergic neurones by muscarinic cholinergic receptors: an in vivo electrophysiological study in the rat. Br J Pharmacol. 1998;124(3):455–464. doi: 10.1038/sj.bjp.0701850
  95. Dickson SL, Hrabovszky E, Hansson C, et al. Blockade of central nicotine acetylcholine receptor signaling attenuate ghrelin-induced food intake in rodents. Neuroscience. 2010;171(4):1180–1186. doi: 10.1016/j.neuroscience.2010.10.005
  96. Jerlhag E, Janson AC, Waters S, et al. Concomitant release of ventral tegmental acetylcholine and accumbal dopamine by ghrelin in rats. PLoS One. 2012;7(11): e49557. doi: 10.1371/journal.pone.0049557
  97. Lacey MG, Calabresi P, North RA. Muscarine depolarizes rat substantia nigra zona compacta and ventral tegmental neurons in vitro through M1-like receptors. J Pharmacol Exp Ther. 1990;253(1):395–400.
  98. Westerink BH, Enrico P, Feimann J, et al. The pharmacology of mesocortical dopamine neurons: a dual-probe microdialysis study in the ventral tegmental area and prefrontal cortex of the rat brain. J Pharmacol Exp Ther. 1998;285(1):143–154.
  99. Miller AD, Blaha CD. Midbrain muscarinic receptor mechanisms underlying regulation of mesoaccumbens and nigrostriatal dopaminergic transmission in the rat. Eur J Neurosci. 2005;21(7): 1837–1846. doi: 10.1111/j.1460-9568.2005.04017.x
  100. Sharf R, McKelvey J, Ranaldi R. Blockade of muscarinic acetylcholine receptors in the ventral tegmental area prevents acquisition of food-rewarded operant responding in rats. Psychopharmacology (Berl). 2006;186(1):113–121. doi: 10.1007/s00213-006-0352-0
  101. Rada PV, Mark GP, Yeomans JJ, et al. Acetylcholine release in ventral tegmental area by hypothalamic self-stimulation, eating, and drinking. Pharmacol Biochem Behav. 2000;65(3):375–379. doi: 10.1016/s0091-3057(99)00218-x
  102. Yeomans JS, Kofman O, McFarlane V. Cholinergic involvement in lateral hypothalamic rewarding brain stimulation. Brain Res. 1985;329(1–2):19–26. doi: 10.1016/0006-8993(85)90508-6
  103. Kofman O, Yeomans JS. Cholinergic antagonists in ventral tegmentum elevate thresholds for lateral hypothalamic and brainstem self-stimulation. Pharmacol Biochem Behav. 1988;31(3): 547–559. doi: 10.1016/0091-3057(88)90229-8
  104. Ikemoto S, Panksepp J. Dissociations between appetitive and consummatory responses by pharmacological manipulations of reward-relevant brain regions. Behav Neurosci. 1996;110(2):331–345. doi: 10.1037//0735-7044.110.2.331
  105. Sakurai T. The neural circuit of orexin (hypocretin): maintaining sleep and wakefulness. Nat Rev Neurosci. 2007;8(3):171–181. doi: 10.1038/nrn2092
  106. Mieda M, Sakurai T. Overview of orexin/hypocretin system. Prog Brain Res. 2012;198:5–14. doi: 10.1016/B978-0-444-59489-1.00002-1
  107. Barson JR, Leibowitz SF. Orexin/Hypocretin System: Role in Food and Drug Overconsumption. Int Rev Neurobiol. 2017;136: 199–237. doi: 10.1016/bs.irn.2017.06.006
  108. Soya S, Sakurai T. Evolution of Orexin Neuropeptide System: Structure and Function. Front Neurosci. 2020;14:691. doi: 10.3389/fnins.2020.00691
  109. Barson JR, Morganstern I, Leibowitz SF. Complementary roles of orexin and melanin-concentrating hormone in feeding behavior. Int J Endocrinol. 2013;2013:983964. doi: 10.1155/2013/983964
  110. Milbank E, López M. Orexins/Hypocretins: Key Regulators of Energy Homeostasis. Front Endocrinol (Lausanne). 2019;10:830. doi: 10.3389/fendo.2019.00830
  111. Kim HY, Hong E, Kim JI, et al. Solution structure of human orexin-A: regulator of appetite and wakefulness. J Biochem Mol Biol. 2004;37(5):565–573. doi: 10.5483/bmbrep.2004.37.5.565
  112. Trivedi P, Yu H, MacNeil DJ, et al. Distribution of orexin receptor mRNA in the rat brain. FEBS Lett. 1998;438(1–2):71–75. doi: 10.1016/s0014-5793(98)01266-6
  113. Hervieu GJ, Cluderay JE, Harrison DC, et al. Gene expression and protein distribution of the orexin-1 receptor in the rat brain and spinal cord. Neuroscience. 2001;103(3):777–797. doi: 10.1016/s0306-4522(01)00033-1
  114. Cluderay JE, Harrison DC, Hervieu GJ. Protein distribution of the orexin-2 receptor in the rat central nervous system. Regul Pept. 2002;104(1–3):131–144. doi: 10.1016/s0167-0115(01)00357-3
  115. Chou TC, Lee CE, Lu J, et al. Orexin (hypocretin) neurons contain dynorphin. J Neurosci. 2001;21(19): RC168. doi: 10.1523/JNEUROSCI.21-19-j0003.2001
  116. Li Y, van den Pol AN. Differential target-dependent actions of coexpressed inhibitory dynorphin and excitatory hypocretin/orexin neuropeptides. J Neurosci. 2006;26(50):13037–13047. doi: 10.1523/JNEUROSCI.3380-06.2006
  117. Chen J, Zhang R, Chen X, et al. Heterodimerization of human orexin receptor 1 and kappa opioid receptor promotes protein kinase A/cAMP-response element binding protein signaling via a Gαs-mediated mechanism. Cell Signal. 2015;27(7):1426–1438. doi: 10.1016/j.cellsig.2015.03.027
  118. Wang C, Wang Q, Ji B, et al. The Orexin/Receptor System: Molecular Mechanism and Therapeutic Potential for Neurological Diseases. Front Mol Neurosci. 2018;11:220. doi: 10.3389/fnmol.2018.00220
  119. Tyree SM, Borniger JC, de Lecea L. Hypocretin as a Hub for Arousal and Motivation. Front Neurol. 2018;9:413. doi: 10.3389/fneur.2018.00413
  120. Winsky-Sommerer R, Yamanaka A, Diano S, et al. Interaction between the corticotropin-releasing factor system and hypocretins (orexins): a novel circuit mediating stress response. J Neurosci. 2004;24(50):11439–11448. doi: 10.1523/JNEUROSCI.3459-04.2004
  121. Toshinai K, Date Y, Murakami N, et al. Ghrelin-induced food intake is mediated via the orexin pathway. Endocrinology. 2003;144(4):1506–1512. doi: 10.1210/en.2002-220788
  122. Yamanaka A, Beuckmann CT, Willie JT, et al. Hypothalamic orexin neurons regulate arousal according to energy balance in mice. Neuron. 2003;38(5):701–713. doi: 10.1016/s0896-6273(03)00331-3
  123. So M, Hashimoto H, Saito R, et al. Inhibition of ghrelin-induced feeding in rats by pretreatment with a novel dual orexin receptor antagonist. J Physiol Sci. 2018;68(2):129–136. doi: 10.1007/s12576-016-0517-5
  124. Macneil DJ. The role of melanin-concentrating hormone and its receptors in energy homeostasis. Front Endocrinol (Lausanne). 2013;4:49. doi: 10.3389/fendo.2013.00049
  125. Konadhode RR, Pelluru D, Shiromani PJ. Neurons containing orexin or melanin concentrating hormone reciprocally regulate wake and sleep. Front Syst Neurosci. 2015;8:244. doi: 10.3389/fnsys.2014.00244
  126. Van den Pol AN, Acuna-Goycolea C, Clark KR, et al. Physiological properties of hypothalamic MCH neurons identified with selective expression of reporter gene after recombinant virus infection. Neuron. 2004;42(4):635–652. doi: 10.1016/s0896-6273(04)00251-x
  127. Rao Y, Lu M, Ge F, et al. Regulation of synaptic efficacy in hypocretin/orexin-containing neurons by melanin concentrating hormone in the lateral hypothalamus. J Neurosci. 2008;28(37): 9101–9110. doi: 10.1523/JNEUROSCI.1766-08.2008
  128. Korotkova TM, Sergeeva OA, Eriksson KS, et al. Excitation of ventral tegmental area dopaminergic and nondopaminergic neurons by orexins/hypocretins. J Neurosci. 2003;23(1):7–11. doi: 10.1523/JNEUROSCI.23-01-00007.2003
  129. Mahler SV, Smith RJ, Moorman DE, et al. Multiple roles for orexin/hypocretin in addiction. Prog Brain Res. 2012;198:79–121. doi: 10.1016/B978-0-444-59489-1.00007-0
  130. Doane DF, Lawson MA, Meade JR, et al. Orexin-induced feeding requires NMDA receptor activation in the perifornical region of the lateral hypothalamus. Am J Physiol Regul Integr Comp Physiol. 2007;293(3): R1022–R1026. doi: 10.1152/ajpregu.00282.2007
  131. Borgland SL, Chang SJ, Bowers MS, et al. Orexin A/hypocretin-1 selectively promotes motivation for positive reinforcers. J Neurosci. 2009;29(36):11215–11225. doi: 10.1523/JNEUROSCI.6096-08.2009
  132. Anand Bk, Brobeck Jr. Localization of a “feeding center” in the hypothalamus of the rat. Proc Soc Exp Biol Med. 1951;77(2):323–324. doi: 10.3181/00379727-77-18766
  133. Sakurai T, Amemiya A, Ishii M, et al. Orexins and orexin receptors: a family of hypothalamic neuropeptides and G protein-coupled receptors that regulate feeding behavior. Cell. 1998;92(4):573–585. doi: 10.1016/s0092-8674(00)80949-6
  134. Dube MG, Kalra SP, Kalra PS. Food intake elicited by central administration of orexins/hypocretins: identification of hypothalamic sites of action. Brain Res. 1999;842(2):473–477. doi: 10.1016/s0006-8993(99)01824-7
  135. Thorpe AJ, Mullett MA, Wang C, et al. Peptides that regulate food intake: regional, metabolic, and circadian specificity of lateral hypothalamic orexin A feeding stimulation. Am J Physiol Regul Integr Comp Physiol. 2003;284(6): R1409–R1417. doi: 10.1152/ajpregu.00344.2002
  136. Thorpe AJ, Kotz CM. Orexin A in the nucleus accumbens stimulates feeding and locomotor activity. Brain Res. 2005;1050(1–2): 156–162. doi: 10.1016/j.brainres.2005.05.045
  137. Thorpe AJ, Teske JA, Kotz CM. Orexin A-induced feeding is augmented by caloric challenge. Am J Physiol Regul Integr Comp Physiol. 2005;289(2): R367–R372. doi: 10.1152/ajpregu.00737.2004
  138. Willie JT, Chemelli RM, Sinton CM, et al. To eat or to sleep? Orexin in the regulation of feeding and wakefulness. Annu Rev Neurosci. 2001;24:429–458. doi: 10.1146/annurev.neuro.24.1.429
  139. Funato H, Tsai AL, Willie JT, et al. Enhanced orexin receptor-2 signaling prevents diet-induced obesity and improves leptin sensitivity. Cell Metab. 2009;9(1):64–76. doi: 10.1016/j.cmet.2008.10.010
  140. Sakurai T. The role of orexin in motivated behaviours. Nat Rev Neurosci. 2014;15(11):719–731. doi: 10.1038/nrn3837
  141. Haynes AC, Jackson B, Chapman H, et al. A selective orexin-1 receptor antagonist reduces food consumption in male and female rats. Regul Pept. 2000;96(1–2):45–51. doi: 10.1016/s0167-0115(00)00199-3
  142. Yamada H, Okumura T, Motomura W, et al. Inhibition of food intake by central injection of anti-orexin antibody in fasted rats. Biochem Biophys Res Commun. 2000;267(2):527–531. doi: 10.1006/bbrc.1999.1998
  143. Hara J, Yanagisawa M, Sakurai T. Difference in obesity phenotype between orexin-knockout mice and orexin neuron-deficient mice with same genetic background and environmental conditions. Neurosci Lett. 2005;380(3):239–242. doi: 10.1016/j.neulet.2005.01.046
  144. Cole S, Mayer HS, Petrovich GD. Orexin/Hypocretin-1 Receptor Antagonism Selectively Reduces Cue-Induced Feeding in Sated Rats and Recruits Medial Prefrontal Cortex and Thalamus. Sci Rep. 2015;5:16143. doi: 10.1038/srep16143
  145. Rodgers RJ, Halford JC, Nunes de Souza RL, et al. SB-334867, a selective orexin-1 receptor antagonist, enhances behavioural satiety and blocks the hyperphagic effect of orexin-A in rats. Eur J Neurosci. 2001;13(7):1444–1452. doi: 10.1046/j.0953-816x.2001.01518.x
  146. Perello M, Sakata I, Birnbaum S, et al. Ghrelin increases the rewarding value of high-fat diet in an orexin-dependent manner. Biol Psychiatry. 2010;67(9):880–886. doi: 10.1016/j.biopsych.2009.10.030
  147. Thorpe AJ, Cleary JP, Levine AS, et al. Centrally administered orexin A increases motivation for sweet pellets in rats. Psychopharmacology (Berl). 2005;182(1):75–83. doi: 10.1007/s00213-005-0040-5
  148. Choi DL, Davis JF, Fitzgerald ME, et al. The role of orexin-A in food motivation, reward-based feeding behavior and food-induced neuronal activation in rats. Neuroscience. 2010;167(1):11–20. doi: 10.1016/j.neuroscience.2010.02.002
  149. Kurose T, Ueta Y, Yamamoto Y, et al. Effects of restricted feeding on the activity of hypothalamic Orexin (OX)-A containing neurons and OX2 receptor mRNA level in the paraventricular nucleus of rats. Regul Pept. 2002;104(1–3):145–151. doi: 10.1016/s0167-0115(01)00340-8
  150. Brown JA, Bugescu R, Mayer TA, et al. Loss of Action via Neurotensin-Leptin Receptor Neurons Disrupts Leptin and Ghrelin-Mediated Control of Energy Balance. Endocrinology. 2017;158(5): 1271–1288. doi: 10.1210/en.2017-00122
  151. Zheng H, Patterson LM, Berthoud HR. Orexin signaling in the ventral tegmental area is required for high-fat appetite induced by opioid stimulation of the nucleus accumbens. J Neurosci. 2007;27(41):11075–11082. doi: 10.1523/JNEUROSCI.3542-07.2007
  152. Petrovich GD, Hobin MP, Reppucci CJ. Selective Fos induction in hypothalamic orexin/hypocretin, but not melanin-concentrating hormone neurons, by a learned food-cue that stimulates feeding in sated rats. Neuroscience. 2012;224:70–80. doi: 10.1016/j.neuroscience.2012.08.036
  153. Di Sebastiano AR, Wilson-Pérez HE, Lehman MN, Coolen LM. Lesions of orexin neurons block conditioned place preference for sexual behavior in male rats. Horm Behav. 2011;59(1):1–8. doi: 10.1016/j.yhbeh.2010.09.006
  154. Harris GC, Wimmer M, Aston-Jones G. A role for lateral hypothalamic orexin neurons in reward seeking. Nature. 2005;437(7058):556–559. doi: 10.1038/nature04071
  155. Nair SG, Golden SA, Shaham Y. Differential effects of the hypocretin 1 receptor antagonist SB334867 on high-fat food self-administration and reinstatement of food seeking in rats. Br J Pharmacol. 2008;154(2):406–416. doi: 10.1038/bjp.2008.3
  156. Sharf R, Sarhan M, Brayton CE, et al. Orexin signaling via the orexin 1 receptor mediates operant responding for food reinforcement. Biol Psychiatry. 2010;67(8):753–760. doi: 10.1016/j.biopsych.2009.12.035
  157. Josselyn SA, Beninger RJ. Neuropeptide Y: intraaccumbens injections produce a place preference that is blocked by cis-flupenthixol. Pharmacol Biochem Behav. 1993;46(3):543–552. doi: 10.1016/0091-3057(93)90542-2
  158. Skibicka KP, Shirazi RH, Hansson C, et al. Ghrelin interacts with neuropeptide Y Y1 and opioid receptors to increase food reward. Endocrinology. 2012;153(3):1194–1205. doi: 10.1210/en.2011–1606
  159. Willesen MG, Kristensen P, Rømer J. Co-localization of growth hormone secretagogue receptor and NPY mRNA in the arcuate nucleus of the rat. Neuroendocrinology. 1999;70(5):306–316. doi: 10.1159/000054491
  160. Hashiguchi H, Sheng Z, et al. Direct versus indirect actions of ghrelin on hypothalamic NPY neurons. PLoS One. 2017;12(9): e0184261. doi: 10.1371/journal.pone.0184261
  161. Hewson AK, Dickson SL. Systemic administration of ghrelin induces Fos and Egr-1 proteins in the hypothalamic arcuate nucleus of fasted and fed rats. J Neuroendocrinol. 2000;12(11):1047–1049. doi: 10.1046/j.1365-2826.2000.00584.x
  162. Wang L, Saint-Pierre DH, Taché Y. Peripheral ghrelin selectively increases Fos expression in neuropeptide Y-synthesizing neurons in mouse hypothalamic arcuate nucleus. Neurosci Lett. 2002;325(1):47–51. doi: 10.1016/s0304-3940(02)00241-0
  163. Verhulst PJ, Janssen S, Tack J, et al. Role of the AMP-activated protein kinase (AMPK) signaling pathway in the orexigenic effects of endogenous ghrelin. Regul Pept. 2012;173(1–3):27–35. doi: 10.1016/j.regpep.2011.09.001
  164. Nakazato M, Murakami N, Date Y, et al. A role for ghrelin in the central regulation of feeding. Nature. 2001;409(6817):194–198. doi: 10.1038/35051587
  165. Fu LY, Acuna-Goycolea C, van den Pol AN. Neuropeptide Y inhibits hypocretin/orexin neurons by multiple presynaptic and postsynaptic mechanisms: tonic depression of the hypothalamic arousal system. J Neurosci. 2004;24(40):8741–8751. doi: 10.1523/JNEUROSCI.2268-04.2004
  166. Schwartz MW, Woods SC, Porte D Jr, et al. Central nervous system control of food intake. Nature. 2000;404(6778):661–671. doi: 10.1038/35007534
  167. van den Pol AN. Weighing the role of hypothalamic feeding neurotransmitters. Neuron. 2003;40(6):1059–1061. doi: 10.1016/s0896-6273(03)00809-2
  168. Saper CB, Chou TC, Elmquist JK. The need to feed: homeostatic and hedonic control of eating. Neuron. 2002;36(2):199–211. doi: 10.1016/s0896-6273(02)00969-8
  169. Cowley MA, Pronchuk N, Fan W, et al. Integration of NPY, AGRP, and melanocortin signals in the hypothalamic paraventricular nucleus: evidence of a cellular basis for the adipostat. Neuron. 1999;24(1):155–163. doi: 10.1016/s0896-6273(00)80829-6
  170. Shimizu N, Oomura Y, Plata-Salamán CR, et al. Hyperphagia and obesity in rats with bilateral ibotenic acid-induced lesions of the ventromedial hypothalamic nucleus. Brain Res. 1987;416(1):153–156. doi: 10.1016/0006-8993(87)91508-3
  171. King BM. The rise, fall, and resurrection of the ventromedial hypothalamus in the regulation of feeding behavior and body weight. Physiol Behav. 2006;87(2):221–244. doi: 10.1016/j.physbeh.2005.10.007
  172. Yousefvand S, Hamidi F. The role of ventromedial hypothalamus receptors in the central regulation of food intake. Int J Pept Res Ther. 2021;27:689–702. doi: 10.1007/s10989-020-10120-9
  173. Cabral A, Fernandez G, Perello M. Analysis of brain nuclei accessible to ghrelin present in the cerebrospinal fluid. Neuroscience. 2013;253:406–415. doi: 10.1016/j.neuroscience.2013.09.008/
  174. Canteras NS, Simerly RB, Swanson LW. Organization of projections from the ventromedial nucleus of the hypothalamus: a Phaseolus vulgaris-leucoagglutinin study in the rat. J Comp Neurol. 1994;348(1):41–79. doi: 10.1002/cne.903480103
  175. Faber CL, Matsen ME, Velasco KR, et al. Distinct Neuronal Projections from the Hypothalamic Ventromedial Nucleus Mediate Glycemic and Behavioral Effects. Diabetes. 2018;67(12):2518–2529. doi: 10.2337/db18-0380
  176. Lo L, Yao S, Kim DW, et al. Connectional architecture of a mouse hypothalamic circuit node controlling social behavior. Proc Natl Acad Sci USA. 2019;116(15):7503–7512. doi: 10.1073/pnas.1817503116
  177. Iigaya K, Minoura Y, Onimaru H, et al. Effects of Feeding-Related Peptides on Neuronal Oscillation in the Ventromedial Hypothalamus. J Clin Med. 2019;8(3):292. doi: 10.3390/jcm8030292
  178. López M, Lage R, Saha AK, et al. Hypothalamic fatty acid metabolism mediates the orexigenic action of ghrelin. Cell Metab. 2008;7(5):389–399. doi: 10.1016/j.cmet.2008.03.006
  179. Minokoshi Y, Alquier T, Furukawa N, et al. AMP-kinase regulates food intake by responding to hormonal and nutrient signals in the hypothalamus. Nature. 2004;428(6982):569–574. doi: 10.1038/nature02440
  180. Xue B, Kahn BB. AMPK integrates nutrient and hormonal signals to regulate food intake and energy balance through effects in the hypothalamus and peripheral tissues. J Physiol. 2006;574(Pt 1): 73–83. doi: 10.1113/jphysiol.2006.113217
  181. Andrews ZB, Liu ZW, Walllingford N, et al. UCP2 mediates ghrelin’s action on NPY/AgRP neurons by lowering free radicals. Nature. 2008;454(7206):846–851. doi: 10.1038/nature07181
  182. Mera P, Mir JF, Fabriàs G, et al. Long-term increased carnitine palmitoyltransferase 1A expression in ventromedial hypotalamus causes hyperphagia and alters the hypothalamic lipidomic profile. PLoS One. 2014;9(5): e97195. doi: 10.1371/journal.pone.0097195
  183. Rau AR, Hentges ST. Energy state alters regulation of proopiomelanocortin neurons by glutamatergic ventromedial hypothalamus neurons: pre- and postsynaptic mechanisms. J Neurophysiol. 2021;125(3):720–730. doi: 10.1152/jn.00359.2020
  184. Yaswen L, Diehl N, Brennan MB, et al. Obesity in the mouse model of pro-opiomelanocortin deficiency responds to peripheral melanocortin. Nat Med. 1999;5(9):1066–1070. doi: 10.1038/12506
  185. Aponte Y, Atasoy D, Sternson SM. AGRP neurons are sufficient to orchestrate feeding behavior rapidly and without training. Nat Neurosci. 2011;14(3):351–355. doi: 10.1038/nn.2739
  186. Zhan C, Zhou J, Feng Q, et al. Acute and long-term suppression of feeding behavior by POMC neurons in the brainstem and hypothalamus, respectively. J Neurosci. 2013;33(8):3624–3632. doi: 10.1523/JNEUROSCI.2742-12.2013
  187. Getting SJ. Targeting melanocortin receptors as potential novel therapeutics. Pharmacol Ther. 2006;111(1):1–15. doi: 10.1016/j.pharmthera.2005.06.022
  188. Baldini G, Phelan KD. The melanocortin pathway and control of appetite-progress and therapeutic implications. J Endocrinol. 2019;241(1): R1–R33. doi: 10.1530/JOE-18-0596
  189. Ellacott KL, Cone RD. The role of the central melanocortin system in the regulation of food intake and energy homeostasis: lessons from mouse models. Philos Trans R Soc Lond B Biol Sci. 2006;361(1471):1265–1274. doi: 10.1098/rstb.2006.1861
  190. Tao YX, Huang H, Wang ZQ, et al. Constitutive activity of neural melanocortin receptors. Methods Enzymol. 2010;484:267–279. doi: 10.1016/B978-0-12-381298-8.00014-9
  191. Kleinau G, Heyder NA, Tao YX, et al. Structural Complexity and Plasticity of Signaling Regulation at the Melanocortin-4 Receptor. Int J Mol Sci. 2020;21(16):5728. doi: 10.3390/ijms21165728
  192. Huszar D, Lynch CA, Fairchild-Huntress V, et al. Targeted disruption of the melanocortin-4 receptor results in obesity in mice. Cell. 1997;88(1):131–141. doi: 10.1016/s0092-8674(00)81865-6
  193. Fan W, Boston BA, Kesterson RA, et al. Role of melanocortinergic neurons in feeding and the agouti obesity syndrome. Nature. 1997;385(6612):165–168. doi: 10.1038/385165a0
  194. Balthasar N, Dalgaard LT, Lee CE, et al. Divergence of melanocortin pathways in the control of food intake and energy expenditure. Cell. 2005;123(3):493–505. doi: 10.1016/j.cell.2005.08.035
  195. Roseberry AG. Altered feeding and body weight following melanocortin administration to the ventral tegmental area in adult rats. Psychopharmacology (Berl). 2013;226(1):25–34. doi: 10.1007/s00213-012-2879-6
  196. Cone RD. Anatomy and regulation of the central melanocortin system. Nat Neurosci. 2005;8(5):571–578. doi: 10.1038/nn1455
  197. Derkach KV, Romanova IV, Shpakov AO. Functional interaction between the dopamine and melanocortin systems in the brain. Russian Journal of Physiology. 2016;102(12):1393–1405.
  198. Micioni Di Bonaventura E, Botticelli L, Tomassoni D, et al. The Melanocortin System behind the Dysfunctional Eating Behaviors. Nutrients. 2020;12(11):3502. doi: 10.3390/nu12113502
  199. Roselli-Rehfuss L, Mountjoy KG, Robbins LS, et al. Identification of a receptor for gamma melanotropin and other proopiomelanocortin peptides in the hypothalamus and limbic system. Proc Natl Acad Sci USA. 1993;90(19):8856–8860. doi: 10.1073/pnas.90.19.8856
  200. Liu H, Kishi T, Roseberry AG, et al. Transgenic mice expressing green fluorescent protein under the control of the melanocortin-4 receptor promoter. J Neurosci. 2003;23(18):7143–7154. doi: 10.1523/JNEUROSCI.23-18-07143.2003
  201. Bagnol D, Lu XY, Kaelin CB, et al. Anatomy of an endogenous antagonist: relationship between Agouti-related protein and proopiomelanocortin in brain. J Neurosci. 1999;19(18): RC26. doi: 10.1523/JNEUROSCI.19-18-j0004.1999
  202. King CM, Hentges ST. Relative number and distribution of murine hypothalamic proopiomelanocortin neurons innervating distinct target sites. PLoS One. 2011;6(10): e25864. doi: 10.1371/journal.pone.0025864
  203. West KS, Lu C, Olson DP, et al. Alpha-melanocyte stimulating hormone increases the activity of melanocortin-3 receptor-expressing neurons in the ventral tegmental area. J Physiol. 2019;597(12):3217–3232. doi: 10.1113/JP277193
  204. Pandit R, Omrani A, Luijendijk MC, et al. Melanocortin 3 Receptor Signaling in Midbrain Dopamine Neurons Increases the Motivation for Food Reward. Neuropsychopharmacology. 2016;41(9):2241–2251. doi: 10.1038/npp.2016.19
  205. Pandit R, van der Zwaal EM, Luijendijk MC, et al. Central melanocortins regulate the motivation for sucrose reward. PLoS One. 2015;10(3): e0121768. doi: 10.1371/journal.pone.0121768
  206. Torre E, Celis ME. Alpha-MSH injected into the substantia nigra or intraventricularly alters behavior and the striatal dopaminergic activity. Neurochem Int. 1986;9(1):85–89. doi: 10.1016/0197-0186(86)90035-5
  207. Torre E, Celis ME. Cholinergic mediation in the ventral tegmental area of alpha-melanotropin induced excessive grooming: changes of the dopamine activity in the nucleus accumbens and caudate putamen. Life Sci. 1988;42(17):1651–1657. doi: 10.1016/0024-3205(88)90444-4
  208. Lindblom J, Opmane B, Mutulis F, et al. The MC4 receptor mediates alpha-MSH induced release of nucleus accumbens dopamine. Neuroreport. 2001;12(10):2155–2158. doi: 10.1097/00001756-200107200-00022
  209. Jansone B, Bergstrom L, Svirskis S, et al. Opposite effects of gamma(1)- and gamma(2)-melanocyte stimulating hormone on regulation of the dopaminergic mesolimbic system in rats. Neurosci Lett. 2004;361(1–3):68–71. doi: 10.1016/j.neulet.2003.12.006
  210. Lindblom J, Kask A, Hägg E, et al. Chronic infusion of a melanocortin receptor agonist modulates dopamine receptor binding in the rat brain. Pharmacol Res. 2002;45(2):119–124. doi: 10.1006/phrs.2001.0913
  211. Lippert RN, Ellacott KL, Cone RD. Gender-specific roles for the melanocortin-3 receptor in the regulation of the mesolimbic dopamine system in mice. Endocrinology. 2014;155(5):1718–1727. doi: 10.1210/en.2013-2049
  212. Beckers S, Zegers D, de Freitas F, et al. Association study of MC4R with complex obesity and replication of the rs17782313 association signal. Mol Genet Metab. 2011;103(1):71–75. doi: 10.1016/j.ymgme.2011.01.007
  213. Berthoud HR. Homeostatic and non-homeostatic pathways involved in the control of food intake and energy balance. Obesity (Silver Spring). 2006;14(Suppl 5):197S-200S. doi: 10.1038/oby.2006.308
  214. Maniam J, Morris MJ. The link between stress and feeding behaviour. Neuropharmacology. 2012;63(1):97–110. doi: 10.1016/j.neuropharm.2012.04.017
  215. Mahler SV, Smith RJ, Aston-Jones G. Interactions between VTA orexin and glutamate in cue-induced reinstatement of cocaine seeking in rats. Psychopharmacology (Berl). 2013;226(4):687–698. doi: 10.1007/s00213-012-2681-5
  216. Nieh EH, Matthews GA, Allsop SA, et al. Decoding neural circuits that control compulsive sucrose seeking. Cell. 2015;160(3): 528–541. doi: 10.1016/j.cell.2015.01.003
  217. Martel P, Fantino M. Mesolimbic dopaminergic system activity as a function of food reward: a microdialysis study. Pharmacol Biochem Behav. 1996;53(1):221–226. doi: 10.1016/0091-3057(95)00187-5
  218. Grigson PS. Like drugs for chocolate: separate rewards modulated by common mechanisms? Physiol Behav. 2002;76(3):389–395. doi: 10.1016/s0031-9384(02)00758-8

© Рейхардт Б.А., Шабанов П.Д., 2022

Creative Commons License
Эта статья доступна по лицензии Creative Commons Attribution 4.0 International License.
 


Согласие на обработку персональных данных с помощью сервиса «Яндекс.Метрика»

1. Я (далее – «Пользователь» или «Субъект персональных данных»), осуществляя использование сайта https://journals.rcsi.science/ (далее – «Сайт»), подтверждая свою полную дееспособность даю согласие на обработку персональных данных с использованием средств автоматизации Оператору - федеральному государственному бюджетному учреждению «Российский центр научной информации» (РЦНИ), далее – «Оператор», расположенному по адресу: 119991, г. Москва, Ленинский просп., д.32А, со следующими условиями.

2. Категории обрабатываемых данных: файлы «cookies» (куки-файлы). Файлы «cookie» – это небольшой текстовый файл, который веб-сервер может хранить в браузере Пользователя. Данные файлы веб-сервер загружает на устройство Пользователя при посещении им Сайта. При каждом следующем посещении Пользователем Сайта «cookie» файлы отправляются на Сайт Оператора. Данные файлы позволяют Сайту распознавать устройство Пользователя. Содержимое такого файла может как относиться, так и не относиться к персональным данным, в зависимости от того, содержит ли такой файл персональные данные или содержит обезличенные технические данные.

3. Цель обработки персональных данных: анализ пользовательской активности с помощью сервиса «Яндекс.Метрика».

4. Категории субъектов персональных данных: все Пользователи Сайта, которые дали согласие на обработку файлов «cookie».

5. Способы обработки: сбор, запись, систематизация, накопление, хранение, уточнение (обновление, изменение), извлечение, использование, передача (доступ, предоставление), блокирование, удаление, уничтожение персональных данных.

6. Срок обработки и хранения: до получения от Субъекта персональных данных требования о прекращении обработки/отзыва согласия.

7. Способ отзыва: заявление об отзыве в письменном виде путём его направления на адрес электронной почты Оператора: info@rcsi.science или путем письменного обращения по юридическому адресу: 119991, г. Москва, Ленинский просп., д.32А

8. Субъект персональных данных вправе запретить своему оборудованию прием этих данных или ограничить прием этих данных. При отказе от получения таких данных или при ограничении приема данных некоторые функции Сайта могут работать некорректно. Субъект персональных данных обязуется сам настроить свое оборудование таким способом, чтобы оно обеспечивало адекватный его желаниям режим работы и уровень защиты данных файлов «cookie», Оператор не предоставляет технологических и правовых консультаций на темы подобного характера.

9. Порядок уничтожения персональных данных при достижении цели их обработки или при наступлении иных законных оснований определяется Оператором в соответствии с законодательством Российской Федерации.

10. Я согласен/согласна квалифицировать в качестве своей простой электронной подписи под настоящим Согласием и под Политикой обработки персональных данных выполнение мною следующего действия на сайте: https://journals.rcsi.science/ нажатие мною на интерфейсе с текстом: «Сайт использует сервис «Яндекс.Метрика» (который использует файлы «cookie») на элемент с текстом «Принять и продолжить».