Alterations in diurnal and nocturnal locomotor activity in rats treated with a monoamine-depleting regimen of methamphetamine or 3,4-methylenedioxymethamphetamine

Rationale: The long-term neurochemical effects produced by the repeated adm inistration of methamphetamine (MA) and 3,4-methylenedioxymethamphetamine ( MDMA) are well documented; however, the functional consequences have not be en clearly defined. Objective: The present study was designed to investigat e whether rats treated with a monoamine-depleting regimen of MA or MDMA exh ibit disturbances in locomotor activity during the diurnal and nocturnal cy cles. Methods: Rats were treated with the vehicle or a monoamine-depleting regimen of MA or MDMA (10 mg/kg, IP, every 2 h for four injections on a sin gle day). One week after drug treatment, the rats were placed in residentia l activity chambers and their locomotor activity was monitored for the next 7-day/night cycles. Results: MA-treated rats exhibited depletions of stria tal dopamine and serotonin content of approximately 70%, whereas MDMA-treat ed rats showed depletions of striatal serotonin content of approximately 50 %. Rats treated with MA demonstrated a significant reduction in diurnal, bu t not nocturnal, locomotor activity, whereas MDMA-treated rats exhibited si gnificant reductions in both diurnal and nocturnal locomotor activity. Anal ysis of the difference in activity between the nocturnal and diurnal cycles revealed that MA-treated animals exhibited a significantly greater change in activity as compared to that observed in vehicle- and MDMA-treated rats. Conclusions: Although it is unknown whether the adaptations in locomotor a ctivity observed in MA- and MDMA-treated rats are due to the loss of dopami ne and/or serotonin, these data suggest that the administration of a monoam ine-depleting regimen of MA or MDMA results in alterations in light-cycle-d ependent locomotor activity.