Interactions of dopaminergic and GABAergic neurotransmission: impact of 6-hydroxydopamine lesions into the substantia nigra of rats.
We have evaluated (a) the effects of dopamine (DA) denervation on gamma-aminobutyric acid (GABA) turnover in terms of in vivo rate of GABA synthesis; (b) effects of DA D1 and D2 receptor agonists and antagonists on the in vivo GABA synthesis rate; and (c) the effects of GABAA and GABAB receptor agonists and antagonists on the intracellular accumulation of cAMP in the ipsi- and contralateral striatum and substantia nigra of rats after unilateral 6-hydroxydopamine-induced lesions of the nigrostriatal DA system (DA depletion > 90%). We observed that the in vivo rate of GABA synthesis remained unaffected when the DA levels were depleted by 95% and 50% in the ipsilateral striatum and substantia nigra, respectively, compared with the contralateral intact side. Basal cAMP levels were increased significantly (92%) in the ipsilateral striatum only, compared with the contralateral intact side. The DA D2 agonist quinpirole (1.0 mg/kg) significantly decreased the rate of GABA formation in the ipsi- and contralateral striatum and substantia nigra. In contrast, the D2 antagonist (+/-)-sulpiride (25.0 mg/kg) augmented the rate of GABA formation in the DA-denervated and intact striatum and substantia nigra. On the other hand, D1 agonist SKF 38393 (10.0 mg/kg) did not affect the GABA synthesis rate. The in vivo rate of GABA synthesis also remained unaffected after administration of D1 antagonist SCH 23390 (1.0 mg/kg) except in the ipsilateral striatum.(ABSTRACT TRUNCATED AT 250 WORDS)
Hossain
M A
MA
Department of Pharmacology, University of Colorado Health Sciences Center, Denver, USA.
Weiner
N
N
D000818:Animals; D001927:Brain Diseases / Q000139:chemically induced / Q000378:metabolism*; D003342:Corpus Striatum / Q000378:metabolism; D000242:Cyclic AMP / Q000378:metabolism; D004298:Dopamine / Q000378:metabolism / Q000502:physiology*; D018491:Dopamine Agonists / Q000494:pharmacology; D018492:Dopamine Antagonists / Q000494:pharmacology; D065127:Dopamine D2 Receptor Antagonists; D058785:GABA-A Receptor Agonists; D058787:GABA-A Receptor Antagonists; D058786:GABA-B Receptor Agonists; D058788:GABA-B Receptor Antagonists; D007424:Intracellular Fluid / Q000378:metabolism; D008297:Male; D016627:Oxidopamine; D051381:Rats; D011916:Rats, Inbred F344; D017447:Receptors, Dopamine D1 / Q000819:agonists / Q000037:antagonists & inhibitors; D017448:Receptors, Dopamine D2 / Q000819:agonists; D013378:Substantia Nigra / Q000378:metabolism / Q000502:physiology*; D009435:Synaptic Transmission / Q000502:physiology*; D005680:gamma-Aminobutyric Acid / Q000096:biosynthesis / Q000378:metabolism / Q000502:physiology*
D018491:Dopamine Agonists; D018492:Dopamine Antagonists; D065127:Dopamine D2 Receptor Antagonists; D058785:GABA-A Receptor Agonists; D058787:GABA-A Receptor Antagonists; D058786:GABA-B Receptor Agonists; D058788:GABA-B Receptor Antagonists; D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2; D005680:gamma-Aminobutyric Acid; D016627:Oxidopamine; D000242:Cyclic AMP; D004298:Dopamine