COCAINE DEPRESSES GABA(A) CURRENT OF HIPPOCAMPAL-NEURONS

Although blockade of dopamine re-uptake and the resulting elevation of excitatory agonists is commonly thought the primary mechanism of coca ine-induced seizures, it is possible that other neurotransmitters such as gamma-aminobutyric acid (GABA) are involved. To examine this possi bility, the effects of cocaine on the whole cell GABA current (I-GABA) of freshly isolated rat hippocampal neurons were investigated with th e patch-clamp technique. Preincubation or acute application of cocaine reversibly suppressed I-GABA. The IC50 was 127 mu M when cocaine was applied before the application of GABA. The concentration-response rel ations of cocaine in various GABA concentrations revealed that cocaine inhibited I-GABA non-competitively. This effect of cocaine appeared t o be independent of voltage. The present study suggests that the GABA receptor/channel complex is also a target for cocaine's action. The su ppression of I-GABA may contribute to cocaine-induced seizures. (C) 19 97 Elsevier Science B.V.