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 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 (1(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 IC₅₀ was 127 μM 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.