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Interactions of dopaminergic and GABAergic neurotransmission: impact of 6-hydroxydopamine lesions into the substantia nigra of rats

MA Hossain and N Weiner

Department of Pharmacology, University of Colorado Health Sciences Center, Denver, USA.

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)

Volume 275, Issue 1, pp. 237-244, 10/01/1995
Copyright © 1995 by American Society for Pharmacology and Experimental Therapeutics




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