Effect of cocaine on responsiveness of alpha(1)-adrenergic receptors in rat cerebral cortex: modulation by GABA-mimetic drugs.

We investigated the effects of single doses of cocaine (10 mg/kg, ip) and the gamma-aminobutyric acid (GABA)-mimetics tiagabine (10 mg/kg, ip) and vigabatrin (150 mg/kg, ip) injected separately or concomitantly with cocaine, on the responsiveness of cerebral cortical alpha(1)-adrenergic receptors. The accumulation of noradrenaline-stimulated inositol phosphates was estimated in vitro at 2 and 24 h after the drug injection. Cocaine significantly enhanced alpha(1)-adrenergic receptor responsiveness to noradrenaline. Neither tiagabine nor vigabatrin influenced the accumulation of inositol phosphates. Finally, the cocaine-evoked augmentation of alpha(1)-adrenoceptor responsiveness was counteracted by tiagabine but not by vigabatrin. This effect may represent a characteristic feature of tiagabine, not necessarily shared by other GABA-mimetic drugs.