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

Serotonin (5-HT) receptor agonists with high affinity for the different sub types (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 behavio rally specific hypophagic effect by accelerating satiety processes; (2) sti mulation 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 e ffect. The present paper reviews studies performed with the relatively sele ctive 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 agoni sts TFMPP (5-HT1B/2C), m-CPP (5-HT2C/1B) and DOI (5-HT2A/2C) in a variety o f 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 ef fects of these compounds, possibly as a function of the administered dose. Studies with 5-HT receptor antagonists indicate that the proposed role of p articular 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 o f ingestive behavior will require extensive pharmacological and behavioral studies, using more selective receptor agonists and antagonists and differe nt behavioral procedures, as well as verification in transgenic animals. (C ) 2000 Elsevier Science Ltd. All rights reserved.