Serotonergic modulation of 3,4-methylenedioxymethamphetamine (MDMA)-elicited reduction of response rate but not rewarding threshold in accumbal self-stimulation.

In a fixed interval 5-s rate-frequency function paradigm with rats, 3,4-methylenedioxymethamphetamine (MDMA; 0.5, 2 and 4 mg/kg) dose-dependently decreased response rate for nucleus accumbens self-stimulation while both D-amphetamine (0.3 and 1 mg/kg) and cocaine (5 and 15 mg /kg) increased response rates. The highest doses of MDMA caused a cessation of responding in many of the rats tested, but in those rats that continued to respond a significant reduction in frequency threshold for self-stimulation was seen. Cocaine and amphetamine dose-dependently reduced frequency threshold in all rats tested. The non-specific serotonin antagonist, methysergide (5 mg/kg), reversed the inhibitory effects of MDMA on response rates and caused all rats to respond following MDMA (4 mg/kg). Methysergide did not affect MDMA's threshold-lowering properties and when administered alone methysergide had not effect on self-stimulation. These results suggest serotonergic involvement in the performance but not reinforcement-modulating effect of MDMA in the self-stimulation paradigm.