Effect of intrastriatal administration of cholinergic and GABAergic agonists on apomorphine-induced circling.

The objectives of this study were (1) to clarify the effects of muscarinic and GABAergic agonists administered directly into the striatum on the circling behavior produced by dopamine (DA) receptor stimulation and (2) to determine whether the effects produced by these drugs are independent or are mediated through an interaction with GABAergic or cholinergic neuronal systems. Circling behavior was produced by the administration of apomorphine (AP) to rats previously injected into their right substantia nigra with 6-hydroxydopamine (6-OHDA). The circling induced by AP (0.5 mg/kg SC) reached a peak rate 5-10 min after injection. The intrastriatal administration of pilocarpine, a muscarinic receptor agonist, 10 min after AP administration produced a dose-dependent inhibition of the AP-induced circling. Similarly, several GABAmimetic drugs (muscimol, GABA, chlordiazepoxide, sodium valproate) also inhibited AP-induced circling in a dose-dependent manner. The intrastriatal administration of scopolamine, which blocks muscarinic cholinergic receptors, reversed the inhibitory effect of pilocarpine but not that of muscimol. However, picrotoxin, the GABAergic antagonist, reversed the inhibitory effect of both pilocarpine and muscimol. These results suggest that the stimulation of either muscarinic or GABAergic receptors in the striatum inhibits the effects of DA receptor stimulation. The inhibitory effect produced by pilocarpine may involve the activation of GABAergic receptors, presumably through stimulation of GABAergic neurons and subsequent release of GABA.