Methylenedioxymethamphetamine depresses glutamate-evoked neuronal firing and increases extracellular levels of dopamine and serotonin in the nucleus accumbens in vivo

Abstract

The nucleus accumbens has been implicated as an important site for the actions of many drugs that are used recreationally. This study examined the effects of methylenedioxymethamphetamine (MDMA), a euphoric and hallucinogenic drug, on glutamate-evoked neuronal firing and on extracellular levels of dopamine and serotonin in the nucleus accumbens of the rat. Microiontophoretic application of MDMA inhibited glutamate-evoked firing of most of the nucleus accumbens cells that were tested (83 of 86), as did microiontophoretic application of dopamine and serotonin. MDMA-induced inhibition of glutamate-evoked firing was partially blocked by the dopamine antagonist SCH39166 and was attenuated by combined pretreatment with inhibitors of both serotonin and catecholamine synthesis, p-chlorophenylalanine and alpha-methyl-p-tyrosine. MDMA applied directly into the nucleus accumbens and adjacent regions of the ventral striatum through a dialysis probe increased extracellular levels of both dopamine and serotonin. These results indicate that MDMA has inhibitory effects on glutamate-evoked neuronal firing in the nucleus accumbens and suggest that the inhibition is mediated by increased extracellular dopamine and serotonin. Furthermore, these results permit MDMA to be added to the extensive list of abused drugs that have been demonstrated to elevate extracellular levels of dopamine and serotonin in the nucleus accumbens.