3,4-methylenedioxymethamphetamine (‘Ecstasy’) promotes the translocation of protein kinase C (PKC): requirement of viable serotonin nerve terminals
H Kenneth Kramer, Jose C Poblete, Efrain C. Azmitia
Brain Research May 1, 1995 DOI: 10.1016/0006-8993(95)00199-z (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | In vivo animal study Peer reviewed |
|---|---|
| Population | Rats (cortical tissue; specific strain, sex, and number not stated) |
| Interventions | MDMA p-chloroamphetamine (PCA) |
| Dose | 20 mg/kg (two injections 10 h apart; also 8 x 20 mg/kg) |
| Duration | Up to 5 days post-treatment |
| Measures | membrane-bound PKC density, [3H]phorbol 12,13 dibutyrate ([3H]PDBu) binding affinity |
| Topics | MDMA Serotonin |
| Citations | 22 |
| Key points | MDMA increased membrane-bound PKC density in rat cortex by 48.0% after two 20 mg/kg injections and produced a lasting increase (up to 5 days) after eight injections, without altering ligand affinity. Prior destruction of cortical serotonin nerve terminals with p-chloroamphetamine blocked this effect, which the authors argue shows that viable serotonin uptake sites are required for MDMA-induced PKC translocation and that prolonged kinase activation may contribute to MDMA's serotonergic neurotoxicity. |
Abstract
The metabolic effects of the neurotoxic, ring-substituted amphetamine 3,4-methylenedioxy-methamphetamine (MDMA or 'Ecstasy') were examined in vivo. In this study, we focused on the ability of MDMA to induce a translocation of the calcium and phospholipid-dependent protein kinase C (PKC) from the cytosol to the cortical plasma membrane. Two injections of MDMA (20 mg/kg; 10 h apart; s.c.) increased the density of membrane bound PKC sites by 48.0% over saline treated animals without mediating a significant change in ligand ([3H]phorbol 12,13 dibutyrate; [3H]PDBu) affinity. Longer drug treatments (8 x 20 mg/kg) induced a lasting (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 are essential for MDMA-induced PKC translocation. These results demonstrate that MDMA-induced PKC translocation is mediated by viable cortical 5-HT nerve terminals, and that prolonged kinase activation may contribute to MDMA-induced serotonergic neurotoxicity.