A 5-HT2C receptor antagonist potentiates a low dose amphetamine-induced conditioned place preference

This study was designed to determine whether a 5-HT2C receptor antagonist could induce a conditioned place preference indicative of reward and/or abuse potential. Here, we present the first evidence that a selective 5-HT2C receptor antagonist, 6-chloro-5-ethoxy-N-(pyridin-2-yl)indoline-1-carboxamide hydrochloride (CEPC), can potentiate a low dose (0.5 mg/kg) amphetamine-induced positive conditioned place preference (CPP). CEPC did not produce any CPP given alone at doses of either 2.0 or 4.0 mg/kg, whereas low dose amphetamine alone produced only a slight, but statistically nonsignificant, place preference. These studies suggest that 5-HT2C receptor antagonists can indirectly potentiate the rewarding effects of amphetamine, and perhaps other psychostimulants. If the results can be translated to man, putative 5-HT2C receptor antagonist treatments for anxiety or depression may enhance or potentiate the rewarding effects of drugs of abuse such as amphetamine, which release dopamine.

► A 5-HT2C antagonist alone did not produce positive conditioned place preference (CPP). ► A selective 5-HT2C antagonist potentiated a low dose amphetamine-induced CPP. ► 5-HT2C antagonists may lack abuse potential, but may potentiate effects of psychostimulants.