Effects of serotonin 5-HT1 and 5-HT2 receptor agonists in a conditioned taste aversion paradigm in the rat

Although 5-HT1/2 receptor agonists can inhibit ingestive behavior, it remai ns unclear whether this effect is confounded by drug-induced "malaise." The present study assessed the potential of such compounds to induce condition ed taste aversion (CTA), a possible correlate of aversive stimulus properti es. Male Wistar rats were tested in a two-bottle saccharin versus water cho ice paradigm. DOI [5-HT2A/2C receptor agonist; ED50 (95% confidence limits) in mg/kg, IP: 0.29 (0.14-0.63)], m-CPP [5-HT2C/1B: 1.69 (0.96-2.99)], TFMP P [5-HT1B/2C; 2.45 (1.46-4.11)], ORG 37684 [5-HT2C; 2.96 (1.17-7.52)], BW 7 23C86 [5-HT2B; 3.49 (1.29-9.47)], CP-94,253 [5-HT1B; 3.74 (1.54-9.08)], and ipsapirone [5-HT1A; 20.15 (11.25-36.09)] dose dependently suppressed sacch arin preference, with potencies that correlated with their previously repor ted potencies to inhibit ingestive behavior in operant- and free feeding pa radigms. Although these results did not necessarily imply that such hypopha gic effects result from a drug-induced "malaise," it can be hypothesized th at they involve, at least partly, the same physiological mechanism/substrat e 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 ac tivation of this substrate results in satiety, whereas strong activation wi ll result in aversive effects, or drug-induced "malaise." (C) 2000 Elsevier Science Inc.