Modulatory Role of Postsynaptic 5-Hydroxytryptamine Type 1A Receptors in (±)-8-Hydroxy-N,N-dipropyl-2-aminotetralin-Induced Hyperphagia in Mice

Brain serotonin (5-HT) is involved in the control of food intake. The ingestive effects of 5-HT are mediated by various receptor subtypes, among others the 5-HT1A receptor. While the involvement of presynaptic 5-HT1A receptors is regarded as certain, the role of postsynaptic 5-HT1A receptors is rather vague. Here, we studied the role of the 5-HT1A receptor on feeding in non-food-deprived and food-deprived (young adult and adult, both sexes) wild-type NMRI mice as well as transgenic NMRI mice, which are characterized by a distinct overexpression of postsynaptic 5-HT1A receptors. The known hyperphagic effect of the 5-HT1A receptor full agonist 8-OH-DPAT ((±)-8-hydroxy-N,N-dipropyl-2-aminotetralin) in non-food-deprived animals was demonstrated in male NMRI wild-type mice and could be antagonized by the selective 5-HT1A receptor antagonist WAY100635. In transgenic mice, this hyperphagic response was induced at lower doses, with an earlier onset and even in females. However, in adult male transgenic mice, the hyperphagic effect did not occur. In food-deprived NMRI wild-type as well as transgenic mice, 8-OH-DPAT first induced a hypophagic and subsequently a hyperphagic effect. Again, in transgenic animals most responses occurred at lower doses and with an earlier onset. The results indicate that postsynaptic 5-HT1A receptors exert a modulatory function in food intake in free-feeding and fasted mice, which for the first time shows an involvement of postsynaptic 5-HT1A receptors in feeding behavior. Understanding the function of pre- and postsynaptic 5-HT1A receptors may help to achieve new insights into the regulation of food intake and foster prospective treatment strategies for eating disorders.