Pharmacological Correction of Alcohol Motivation Depends on the Phenotype of the Response to Emotional Stress

Abstract

The specific features of alcohol behavior were studied in MR and MNRA rats that exhibit an opposite reaction to emotional stress. We evaluated the effect of a dipeptide anxiolytic GB-115 (N-phenyl-hexanoyl-glycyl-L-tryptophan amide, neuropeptide cholecystokinin-4 analogue with antagonistic activity) on alcohol motivation in rats, which was formed over 12 months. High-emotionality MR rats were more sensitive to the anxiolytic effect of ethanol in the conflict situation test than low-emotionality MNRA rats. MNRA rats consumed a greater amount of ethanol under a free-choice condition with 15% ethanol solution and water (as in comparison with MR rats). However, the behavior of MR rats was transformed due to a significant increase in alcohol motivation from the 5th month of long-term free access to ethanol. An anxiolytic GB-115 (0.025 mg/kg intraperitoneally for 14 days) with selective activity in high-emotionality rats was shown to reduce significantly the average daily consumption and alcohol-deprivation effect in MR rats, but did not modulate ethanol addiction in MNRA rats.