5-HT1A/5-HT7 receptor interplay: Chronic activation of 5-HT7 receptors decreases the functional activity of 5-HT1A receptor and its сontent in the mouse brain

Abstract

Serotonin receptors 5-HT_1A and 5-HT₇ are involved in the development of various psychopathologies. Some data indicate that there is an interplay between 5-HT_1A 5-HT₇ receptors that could be implicated in the regulation of their function. This work analyzed the effects of chronic 5-HT₇ activation on the functional activity of 5-HT₇ and 5-HT_1A receptors, on the corresponding protein levels, and on the expression of genes encoding 5-HT₇ and 5-HT_1A receptors in the mouse brain. Chronic administration of the 5-HT₇ selective agonist LP44 (20.5 nmol, i.c.v., 14 days) produced considerable desensitization of both 5-HT₇ and 5-HT_1A receptors. In LP44-treated mice, the hypothermic responses mediated by both 5-HT₇ and 5-HT_1A receptors were attenuated. Moreover, the levels of 5-HT_1A receptor protein in the midbrain and the frontal cortex of LP44-treated mice were significantly decreased. However, the brain levels of 5-HT₇ receptor protein did not differ between LP44-treated and control mice. Chronic LP44 treatment did not alter the expression of the 5-HT₇ and 5-HT_1A receptor genes in all investigated brain structure. These data suggest that 5-HT₇ receptors participate in the posttranscriptional regulation of the 5-HT_1A receptors functioning.