The effects of the 5-HT3 receptor antagonist tropisetron on cocaine-induced conditioned taste aversions

Abstract

Although cocaine readily induces taste aversions, little is known about the mechanisms underlying this effect. Recent work has shown that cocaine's actions on serotonin (5-HT) may be involved. To address this possibility, the present experiments examined a role of the specific 5-HT receptor, 5-HT3, in this effect given that it is implicated in a variety of behavioral effects of cocaine. This series of investigations first assessed the aversive effects of the 5-HT3 receptor antagonist tropisetron alone (Experiment 1). Specifically, in Experiment 1 male Sprague–Dawley rats were given repeated pairings of a novel saccharin solution and tropisetron (0, 0.056, 0.18 and 0.56mg/kg). Following this, a non-aversion-inducing dose of tropisetron (0.18mg/kg) was assessed for its ability to block aversions induced by a range of doses of cocaine (Experiment 2). Specifically, in Experiment 2 animals were given access to a novel saccharin solution and then injected with tropisetron (0 or 0.18mg/kg) followed by an injection of various doses of cocaine (0, 10, 18 and 32mg/kg). Cocaine induced dose-dependent taste aversions that were not blocked by tropisetron, suggesting that cocaine's aversive effects are not mediated by 5-HT, at least at this specific receptor subtype. At the intermediate dose of cocaine, aversions appeared to be potentiated, suggesting 5-HT3 may play a limiting role in cocaine's aversive effects. These data are discussed in the context of previous examinations of the roles of serotonin, dopamine, and norepinephrine in cocaine-induced aversions.