Effects of serotonin 5-HT(1) and 5-HT(2) receptor agonists in a conditioned taste aversion paradigm in the rat

Although 5-HT(1/2) receptor agonists can inhibit ingestive behavior, it remains unclear whether this effect is confounded by drug-induced "malaise." The present study assessed the potential of such compounds to induce conditioned taste aversion (CTA), a possible correlate of aversive stimulus properties. Male Wistar rats were tested in a two-bottle saccharin versus water choice paradigm. DOI [5-HT(2A/2C) receptor agonist; ED(50) (95% confidence limits) in mg/kg, IP: 0.29 (0.14-0.63)], m-CPP [5-HT(2C/1B); 1.69 (0.96-2.99)], TFMPP [5-HT(1B/2C); 2.45 (1.46-4.11)], ORG 37684 [5-HT(2C); 2.96 (1. 17-7.52)], BW 723C86 [5-HT(2B); 3.49 (1.29-9.47)], CP-94,253 [5-HT(1B); 3.74 (1.54-9.08)], and ipsapirone [5-HT(1A); 20.15 (11. 25-36.09)] dose dependently suppressed saccharin preference, with potencies that correlated with their previously reported potencies to inhibit ingestive behavior in operant- and free feeding paradigms. Although these results did not necessarily imply that such hypophagic effects result from a drug-induced "malaise," it can be hypothesized that they involve, at least partly, the same physiological mechanism/substrate underlying CTA. As the hypophagic effects of serotonergic compounds have been ascribed to their effects on satiety processes and generally occur at doses that are lower than those inducing CTA, it is speculated that weak activation of this substrate results in satiety, whereas strong activation will result in aversive effects, or drug-induced "malaise."