The effect of gamma-acetylenic GABA, an enzyme-activated irreversible inhibitor of GABA-transaminase, on dopamine pathways of the extrapyramidal and limbic systems.
gamma-Acetylenic GABA (100 mg/kg i.p.) inhibited GABA-transaminase activity and caused a several-fold increase in the concentration of GABA in rat brain. This increased GABA concentration was associated with a decreased rate of dopamine depletion following alpha-methyl-p-tyrosine treatment and a decrease in homovanillic acid in extrapyramidal and limbic structures suggesting a decrease in dopamine turnover in both pathways. In addition, gamma-acetylenic GABA injected into the ventral mesencephalic tegmentum decreased dopamine turnover in the mesolimbic forebrain. These results are consistent with a modulatory function of GABAergic neurons on extrapyramidal and limbic dopamine pathways. Inhibitory effects on dopaminergic functions of the extrapyramidal and limbic systems were also indicated by the amphetamine and apomorphine-induced ipsilateral turning after unilateral substantia nigral injections of gamma-acetylenic GABA and by the attenuation of dopamine-induced hypermotility after bilateral injections of gamma-acetylenic GABA into the nucleus accumbens.
D000612:4-Aminobutyrate Transaminase / Q000037:antagonists & inhibitors*; D000614:Aminocaproates / Q000494:pharmacology*; D000818:Animals; D002395:Catecholamines / Q000378:metabolism; D004298:Dopamine / Q000502:physiology*; D005116:Extrapyramidal Tracts / Q000187:drug effects*; D006719:Homovanillic Acid / Q000378:metabolism; D008032:Limbic System / Q000187:drug effects*; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D051381:Rats; D000637:Transaminases / Q000037:antagonists & inhibitors*
D000614:Aminocaproates; D002395:Catecholamines; D000637:Transaminases; D000612:4-Aminobutyrate Transaminase; D004298:Dopamine; D006719:Homovanillic Acid