Cocaine depresses GABAA current of hippocampal neurons.

Abstract Although blockade of dopamine re-uptake and the resulting elevation of excitatory agonists is commonly thought the primary mechanism of cocaine-induced seizures, it is possible that other neurotransmitters such as γ -aminobutyric acid (GABA) are involved. To examine this possibility, the effects of cocaine on the whole cell GABA current ( I GABA ) of freshly isolated rat hippocampal neurons were investigated with the patch-clamp technique. Preincubation or acute application of cocaine reversibly suppressed I GABA . The IC 50 was 127 μ M when cocaine was applied before the application of GABA. The concentration-response relations of cocaine in various GABA concentrations revealed that cocaine inhibited I GABA non-competitively. This effect of cocaine appeared to be independent of voltage. The present study suggests that the GABA receptor/channel complex is also a target for cocaine's action. The suppression of I GABA may contribute to cocaine-induced seizures.