5-HT3 receptor antagonists block cocaine- and methamphetamine-induced place preference.

The effects of 5-HT3 receptor antagonists, MDL72222 and ICS205-930, on cocaine- and methamphetamine-induced place preference were examined. Cocaine (0.5-4.0 mg/kg, ip) and methamphetamine (0.25-2.0 mg/kg, ip) induced a dose-dependent place preference. The cocaine (4 mg/kg)-induced place preference was blocked by both MDL72222 and ICS205-930 (0.1 mg/kg, ip). On the other hand, the dose (0.1 mg/kg) of 5-HT3 antagonists did not block the methamphetamine (2 mg/kg)-induced place preference, although a higher dose (1.0 mg/kg) of 5-HT3 receptor antagonists did block it. The difference in sensitivity may reflect a difference in attack point in dopaminergic system of these two psychostimulants. Our findings suggest that the rewarding effects of cocaine and methamphetamine may be indirectly regulated by 5-HT3 receptor; cocaine being more sensitive to 5-HT3 receptor antagonists than methamphetamine.