Prior exposure to methylenedioxyamphetamine (MDA) induces serotonergic loss and changes in spontaneous exploratory and amphetamine-induced behaviors in rats

The substituted amphetamine 3,4 methylenedioxyamphetamine (MDA) is a popula r recreational drug of abuse. Administration of MDA to experimental animals has been shown to induce damage to serotonergic axons and nerve terminals. However, there is a lack of information on whether these treatments can pr oduce any long-term changes in behavioural performance particularly under s tressful conditions. In the present study, MDA (7.5 mg/kg; i.p.) was admini stered twice daily to adult male Sprague Dawley rats for four days. Four we eks following the last dose, spontaneous behaviors of these animals were tr acked and scored in a novel "open field" environment using an automated vid eo registration and computer interpretation system. Changes in behavior wer e observed in MDA treated animals including reductions in exploratory orien ted behaviors (locomotion and rearing) and increases in grooming behavior w hen compared to vehicle treated controls. MDA-treated animals also displaye d an enhanced locomotor and stereotyped response to d-amphetamine (12 mg/kg ; i.p.). Significant reductions in 5-HT concentrations (20-30%) were observ ed in the frontal cortex, amygdala, striatum, and hypothalamus as a result of MDA treatment. In addition, [H-3] paroxetine binding was reduced by (40% ) in the cortex of MDA treated rats indicating that the decrease in 5-HT co ncentrations were accompanied by a reduction in intact presynaptic 5-HT ner ve terminals. Changes in behavioural performance in a novel "open field" en vironment and following d-amphetamine challenge might be considered as a be havioural model of serotonergic deficit induced by MDA. The findings of thi s study also suggest that MDA use may increase both the abuse potential, an d the propensity to develop psychosis as a result of abusing other psychost imulants such as d-amphetamine. (C) 2001 Elsevier Science Inc. All rights r eserved.