Cocaine and lidocaine have additive inhibitory effects on the GABAA current of acutely dissociated hippocampal pyramidal neurons.

Inhibition mediated by gamma-aminobutyric acid (GABA) is a major target for the central actions of cocaine and lidocaine, which can result in seizures, especially when these drugs are abused in combination. In the present study, we investigated how cocaine and lidocaine interact to depress GABA current (IGABA), recorded by the whole-cell technique in freshly isolated rat hippocampal neurons. Cocaine depressed IGABA in a concentration dependent manner, such that cocaine was more potent against lower than higher GABA concentrations: the cocaine IC50 was 0.13, 0.62 and 1.2 mM for GABA at 2, 10 and 100 microM, respectively. Cocaine depressed IGABA to the same extent in the absence and presence of 1 microM tetrodotoxin, indicating that cocaine inhibition of IGABA is distinct from its Na+ channel blocking action. Lidocaine reversibly depressed IGABA evoked by 10 microM GABA, with an IC50 of 9.8 mM. In the presence of 3 mM lidocaine, 0.3 mM cocaine depressed IGABA (10 microM GABA) to 30+/-7%. The significantly greater depression by the combined agents (p<0.05) indicates additive effects on the GABA receptor/channel complex, which are likely to contribute to the additive convulsant effects noted when these drugs are abused in combination. Copyright 1999 Elsevier Science B.V.