3,4-METHYLENEDIOXYMETHAMPHETAMINE (ECSTASY) PROMOTES THE TRANSLOCATION OF PROTEIN-KINASE-C (PKC) - REQUIREMENT OF VIABLE SEROTONIN NERVE-TERMINALS

The metabolic effects of the neurotoxic, ring-substituted amphetamine 3,4-methylenedioxy-methamphetamine (MDMA or 'Ecstasy') were examined i n vivo. In this study, we focused on the ability of MDMA to induce a t ranslocation of the calcium and phospholipid-dependent protein kinase C (PKC) from the cytosol to the cortical plasma membrane. Two injectio ns of MDMA (20 mg/kg; 10 h apart; s.c.) increased the density of membr ane bound PKC sites by 48.0% over saline treated animals without media ting a significant change in ligand ([H-3]phorbol 12,13 dibutyrate; [H -3]PDBu) affinity. Longer drug treatments (8 X 20 mg/kg) induced a las ting (up to 5 days post-treatment) increase in the density of membrane -bound PKC. Prior destruction of cortical 5-HT nerve terminals with p- chloroamphetamine (PCA) prevents this effect and suggests that viable 5-HT uptake sites we essential for MDMA-induced PKC translocation. The se results demonstrate that MDMA-induced PKC translocation Is mediated by viable cortical 5-HT nerve terminals, and that prolonged kinase ac tivation may contribute to MDMA-induced serotonergic neurotoxicity.