Dopaminergic inhibition of striatal GABA release after 6-hydroxydopamine.
We have examined the regulation of striatal GABA release by endogenous dopamine in rats with partial degeneration of dopamine-containing neurons. 6-Hydroxydopamine was administered into the lateral ventricles or medial forebrain bundle. Either 3 days or 3 weeks later, slices of neostriatum were prepared, preloaded with [3H]GABA, and superfused in order to measure [3H]GABA overflow in response to electrical stimulation (8 Hz). The loss of dopaminergic terminals was estimated by measuring tissue levels of dopamine. The impact of endogenous dopamine on [3H]GABA was evaluated by measuring the ability of sulpiride, a D2 dopamine receptor antagonist, to increase the depolarization-induced [3H]GABA overflow. In non-treated or vehicle-pretreated rat neostriatum, sulpiride (10 microM) increased the depolarization-induced [3H]GABA overflow to 193% of control. Three days after lesioning, the stimulatory effect of sulpiride on [3H]GABA overflow was identical to that seen in control rats so long as the loss of tissue dopamine did not exceed 60%, although with larger lesions the sulpiride-induced response was reduced. Three weeks after lesioning, however, the stimulatory effect of sulpiride on electrically evoked [3H]GABA overflow remained at the level seen in control tissue even in cases where tissue dopamine was reduced to 13% of normal. In contrast, no sulpiride-induced increase in [3H]GABA overflow was detected 3 weeks after nearly complete lesions with reduced tissue dopamine to 20% of normal. These data suggest that short- and long-term compensatory changes maintain dopaminergic control over GABAergic projection neurons and interneurons until the loss of dopamine innervation is almost complete.
Harsing
L G
LG
Department of Neuroscience, University of Pittsburgh, PA 15260, USA.
Zigmond
M J
MJ
D000818:Animals; D003342:Corpus Striatum / Q000187:drug effects* / Q000378:metabolism*; D004298:Dopamine / Q000502:physiology*; D018492:Dopamine Antagonists / Q000494:pharmacology; D004558:Electric Stimulation; D008297:Male; D016627:Oxidopamine / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013469:Sulpiride / Q000494:pharmacology; D013997:Time Factors; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
D018492:Dopamine Antagonists; D005680:gamma-Aminobutyric Acid; D013469:Sulpiride; D016627:Oxidopamine; D004298:Dopamine