Effects of MDMA administration on scopolamine-induced disruptions of learning and performance in rats

Functional deficits following short-course high-dose administration of 3,4-methylenedioxymethamphetamine (MDMA) have been difficult to characterize despite evidence indicating that MDMA is neurotoxic in several species. Therefore, the present research used rats trained to respond under a complex behavioral procedure (i.e., a multiple schedule of repeated acquisition and performance of response chains), pharmacological challenge with scopolamine and neurotransmitter assays to examine the effects of MDMA neurotoxicity on learning. Prior to MDMA administration, 0.032-0.32 mg/kg of scopolamine produced dose-dependent rate-decreasing and error-increasing effects in both components of the multiple schedule. Administration of 10 mg/kg of MDMA twice per day for 4 days also produced rate-decreasing and error-increasing effects on these days, but responding returned to baseline levels several days after the final injection. In contrast to the recovery of responding, this regimen of MDMA in untrained rats significantly reduced levels of both serotonin and its major metabolite, 5-hydroxyindoleacetic acid (5-HIAA), for 13-14 days. Furthermore, the rate-decreasing and error-increasing effects of scopolamine were significantly attenuated after MDMA treatment. These results indicate that certain complex operant behaviors rapidly recover from the effects of short-course high-dose MDMA administration, despite the reduced levels of serotonin in the central nervous system (CNS), and that this MDMA-induced loss of serotonin may affect cholinergic transmission.