3,4-Methylenedioxymethamphetamine enhances the release of acetylcholine in the prefrontal cortex and dorsal hippocampus of the rat

Rationale The neurochemical effects produced by acute administration of 3,4-methylenedioxymethamphetamine (MDMA) on the monoaminergic systems in the brain are well documented; however, there has been little consideration of the potential effects of MDMA on other neurotransmitter systems. Objective The present study was designed to investigate the acute effect of MDMA on cholinergic neurons by measuring acetylcholine (ACh) release in the medial prefrontal cortex (PFC) and dorsal hippocampus, terminal regions of cholinergic projection neurons originating in the basal forebrain. Methods In vivo microdialysis and high-performance liquid chromatography with electrochemical detection (HPLC-ED) were used to assess the effects of MDMA on the extracellular concentration of ACh in the PFC and dorsal hippocampus of the rat. Results The systemic administration of MDMA (3–20 mg/kg, i.p.) resulted in an increased extracellular concentration of ACh in the PFC and dorsal hippocampus. Reverse dialysis of MDMA (100 μM) into the PFC and hippocampus also increased ACh release in these brain regions. Treatment with parachlorophenylalanine and α-methyl-para-tyrosine, inhibitors of serotonin (5-HT) and dopamine (DA) synthesis, respectively, significantly attenuated the release of ACh stimulated by MDMA in the PFC, but not in the dorsal hippocampus. Conclusions MDMA exerts a stimulatory effect on the release of ACh in the PFC and dorsal hippocampus in vivo, possibly by mechanisms localized within these brain regions. In addition, these results suggest that the MDMA-induced release of ACh in the PFC involves both serotonergic and dopaminergic mechanisms.