Striatal dopamine release and contraversive rotation elicited by intranigrally applied muscimol

Abstract

SEVERAL lines of evidence indicate that release of dopamine (DA) within the corpus striatum mediates turning behaviour in the rat^1,2. The turning occurs in a direction away from the striatum with the greatest activation of DA neurones. Contraversive turning also occurs after unilateral microinjection of agonists of γ-aminobutyric acid (GABA) into the substantia nigra (SN)^3–6, the site of origin of the dopaminergic nigrostriatal pathway. This finding was unexpected, as GABA inhibits neurones^7,8 thought to be DA-containing cells9,10 in the SN. Hence, a GABA agonist would be expected to cause a decrease in the rate of release of striatal DA on the microinjected side and result in ipsiversive turning. Therefore, it is unclear whether a GABA agonist applied to the SN alters DA release in the ipsilateral striatum to evoke turning, or whether the turning results from a non-dopaminergic mechanism⁵. The dopamine antagonist, haloperidol, has been reported either to reduce significantly^3,6 or exert no action on^4,5 the contraversive turning response evoked by intranigral injection of a GABA-like compound. To clarify the action of GABA on the nigrostriatal dopaminergic system, we examined the effect of muscimol, a potent GABA agonist¹¹, on striatal DA metabolism and release. We report here that intraperitoneally (i.p.) administered muscimol increases the concentration of striatal homovanillic acid (HVA) and that intranigral perfusion of muscimol simultaneously evokes both contraversive turning and DA release from the ipsilateral striatum.