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.
Wieczerzak
Krzysztof
K
Department of Brain Biochemistry, Institute of Pharmacology, Polish Academy of Science, Smetna 12, PL 31-343 Kraków, Poland.
Witarski
Tadeusz
T
Kowalska
Marta
M
Nawrat
Dominika
D
Roman
Adam
A
Bielawski
Adam
A
Nalepa
Irena
I
D000818:Animals; D002540:Cerebral Cortex / Q000187:drug effects* / Q000502:physiology; D003042:Cocaine / Q000494:pharmacology*; D007295:Inositol Phosphates / Q000378:metabolism; D008297:Male; D009557:Nipecotic Acids / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D018340:Receptors, Adrenergic, alpha-1 / Q000502:physiology*; D000078308:Tiagabine; D020888:Vigabatrin / Q000494:pharmacology*
D007295:Inositol Phosphates; D009557:Nipecotic Acids; D018340:Receptors, Adrenergic, alpha-1; D020888:Vigabatrin; D003042:Cocaine; D000078308:Tiagabine