MICRODIALYSIS STUDIES ON 3,4-METHYLENEDIOXYAMPHETAMINE AND STRUCTURALLY RELATED ANALOGS

The acute effect of 3,4-methylenedioxyamphetamine (MDA) and three structural analogues on the extracellular concentrations of dopamine (DA) and its major metabolites, dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA), in the striatum was studied using in vivo microdialysis in awake, freely moving rats. MDA significantly (P < 0.001) increased and decreased the extracellular concentrations of DA and its metabolites, respectively, following i.p. administration. Similarly, acute administration of the N-methyl (MDMA) and N-ethyl (MDE) derivatives of MDA significantly (P < 0.05) increased the concentration of DA in the striatum. The alpha-ethyl homologue of MDMA, MBDB, increased the extracellular concentration of DA but significantly (P < 0.05) less than MDA, MDMA or MDE. The rank order of potency for these amphetamine derivatives to increase the extracellular concentration of DA was: MDA > MDMA > MDE > MBDB > vehicle. The increase in extracellular DA concentration following a single administration of these compounds was negatively correlated with the level of serotonin (5-HT) and its major metabolite, 5-hydroxyindoleacetic acid (5-HIAA) in the contralateral striatum measured 7 days following drug administration. Thus, extending the alkyl group on the nitrogen or alpha-carbon of MDA reduces the ability of these compounds both to increase acutely the extracellular concentration of DA and to produce long-lasting depletions of 5-HT in the brain.