Neonatal 3,4-methylenedioxymethamphetamine (MDMA) exposure alters neuronal protein kinase A activity, serotonin and dopamine content, and [35S]GTPgammaS binding in adult rats

Recreational use of methylenedioxymethamphetamine (MDMA) has dramatically increased among juveniles and young adults of child-bearing age, and the potential for fetal exposure has increased. For this reason, it is surprising that comparatively few studies have assessed the long-term impact of early MDMA exposure on serotonin (5-HT) and dopamine (DA) neurotransmitter systems. The purpose of this study was to determine whether repeated exposure to MDMA during the preweanling period would cause long-term changes in 5-HT and DA functioning. Rats were treated with saline or 20 mg/kg MDMA (two injections per day) from postnatal day (PD) 11-20. At PD 90, rats were killed, and their dorsal striatum, prefrontal cortex, and hippocampus were removed. 5-HT and DA content, as well as their metabolites, were measured using HPLC. In addition, cAMP-dependent protein kinase A (PKA) activity and agonist-stimulated 35S]GTPgammaS binding was assayed using tissue homogenates from each brain region. Results indicated that early MDMA exposure caused a decrease in PKA activity and 5-HT content in the prefrontal cortex and hippocampus while increasing the efficacy of 5-HT1A receptors as measured by agonist-stimulated 35S]GTPgammaS binding. Additionally, DA content was reduced in the dorsal striatum and prefrontal cortex. These data indicate that early MDMA exposure has long-term effects on the 5-HT and DA neurotransmitter systems that may be mediated, at least partially, by changes in 5-HT1A receptor sensitivity.