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

The 5-HT1A agonist, 8-hydroxy-2-(di-n-propylamino) tetralin (8-OH-DPAT) at a 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-HT1A, 5-HT1B, 5-HT1C 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 suggests that the 5-HT1C site is not involved as it has high affinity for both 5-HT2 and 5-HT1C receptors. Blockade of the hyperphagia by spiperone suggests mediation by 5-HT1A rather than 5-HT1B receptors. Although spiperone also blocks dopamine and alpha 2-adrenoreceptors, involvement of these sites is unlikely as neither the DA antagonist haloperidol nor the alpha 2-adrenoceptor antagonist idazoxan blocked 8-OH-DPAT-induced feeding. These results indicate that 8-OH-DPAT-induced feeding is mediated by 5-HT1A receptors.