Evidence that the hyperphagic response to 8-OH-DPAT is mediated by 5-HT1A receptors

The 5-HT_1A agonist, 8-hydroxy-2-(di-n-propylamino) tetralin (8-OH-DPAT) at dose of 1 mg/kg s.c. increased food intake in free feeding rats. 8-OH-DPAT-induced feeding was blocked by metergoline which has comparable affinity for 5-HT_1A, 5-HT_1B, 5-HT_1C and 5-HT₂ receptors. This is consistent with the hyperphagia being mediated by an action at 5-HT receptors. Evidence against the involvement of 5-HT₂ or 5-HT₃ receptors was provided by the lack of effect of methysergide, ketanserin, MDL 72222 and ICS 205930 on the feeding response. Blockade of the hyperphagia by (−)- but not (+)pendolol which stereoselectively interacts with 5-HT₁ receptors indicated an involvement of this receptor type. The lack of effect of ketanserin suggest that the 5-HT_1C site is not involved as it has high affinity for both 5-HT₂ and 5-HT_1C receptors. Blockade of the hyperphagia by spiperone suggest mediation by 5-HT_1A rather than 5-HT_1B receptors. Although spiperone also blocks dopamine and ₂-adrenoreceptors, involvement of these sites is unlikely as neither the DA antagonist haloperidol nor the ₂-adrenoceptor antagonist idazoxan blocked 8-OH-DPAT-included feeding. These results indicate that 8-OH-DPAT-induced feeding is mediated by 5-HT_1A receptors.