Effects of selected serotonin 5-HT1 and 5-HT2 receptor agonists on feeding behavior:: possible mechanisms of action

Serotonin (5-HT) receptor agonists with high affinity for the different subtypes (i.e. 5-HT1A-1F, 5-HT2A-2C) of the 5-HT1- and 5-HT2 receptor families have been shown to affect ingestive behavior. It has been assumed that: (1) stimulation of hypothalamic 5-HT2C or 5-HT1B receptors leads to a behaviorally specific hypophagic effect by accelerating satiety processes; (2) stimulation of 5-HT2A receptors leads to a disruption of the feeding cascade; and (3) stimulation of 5-HT1A and 5-HT2B receptors leads to a hyperphagic effect. The present paper reviews studies performed with the relatively selective receptor agonists ipsapirone (5-HT1A), CP-94,253 (5-HT1B), BW 723C86 (5-HT2B) and ORG 37684 (5-HT2C), as well as the nonselective receptor agonists TFMPP (5-HT1B/2C), m-CPP (5-HT2C/1B) and DOI (5-HT2A/2C) in a variety of feeding paradigms in rats, both after systemic and local injection. These studies support a role for other neuroanatomical regions (i.e. brain stem) and behavioral mechanisms (i.e. appetitive processes) in the hypophagic effects of these compounds, possibly as a function of the administered dose. Studies with 5-HT receptor antagonists indicate that the proposed role of particular 5-HT1/2 receptor subtypes in the hypophagic effects of these 5-HT receptor agonists may be more complicated than originally thought, Further characterization of the role of 5-HT1/2 receptor subtypes in the control of ingestive behavior will require extensive pharmacological and behavioral studies, using more selective receptor agonists and antagonists and different behavioral procedures, as well as verification in transgenic animals. (C) 2000 Elsevier Science Ltd. All rights reserved.