Amphetamine-induced circling behavior in rats: effects of unilateral microinjections of GABA and GABA-related drugs into substantia nigra.

In these experiments, the GABA control upon dopaminergic nigrostriatal neurons has been investigated using circling behavior in the rat. Chronically cannulated rats were given D-amphetamine (2 mg/kg i.p.) 45 min before unilateral microinjection (0.2 microliter/2 min) into the substantia nigra (SN) of GABA, muscimol, chlordiazepoxide (CDP) or bicuculline. Circling behavior was continuously recorded for 165 min using an automated rotometer. (1) Non-microinjected control rats exhibit a 'spontaneous' circling behavior after amphetamine. (2) When applied to the SN contralateral to the preferential side of the 'spontaneous' rotations, saline enhances contraversive circling; GABA (5 X 10(-5)M), CDP (5 X 10(-5)M) and muscimol (5 x 10(-7)M, 5 X 10(-8)M) counteract this effect and induce (except CDP) light ipsiversive rotations; GABA (10(-2)M) and muscimol (5 x 10(-5)M) further enhance contraversive turning. (3) When applied to the SN ipsilateral to the preferential side of the 'spontaneous' rotations, saline has no marked effect on the ipsiversive circling behavior but induces weak contraversive turning; GABA (5 X 10(-5)M), CDP (5 X 10(-5)M) and muscimol (5 x 10(-8)M) enhance the ipsiversive rotations; GABA (10(-2)M) and muscimol (5 x 10(-5)M) transiently decrease the ipsiversive circling; bicuculline (5 x 10(-5)M) induces a vigorous contraversive turning associated with a transient inhibition of the ipsiversive rotations. These results suggest that the activity of the nigral neurons is presumably stimulated by the microinjection itself, by bicuculline and, to a lesser extent, by high concentrations of GABA and muscimol, and inhibited by low concentrations of GABA, muscimol and CDP. These findings could further support the hypotheses of a GABAergic inhibitory control upon DA nigrostriatal pathways and of a GABA-like activity of CDP.