Regulation of nigro-striatal dopaminergic neurotransmission in the rat

Abstract

Abstract The activity of the rat nigro-striatal dopaminergic system has been studied after unilateral injections of ethanolamine O-sulphate (EOS) (200 μg kg −1 ) into the substantia nigra, zone reticulata and after discrete electrolytic lesions in the same area. Twenty-four hr after EOS pretreatment, GABA-T activity was significantly reduced and the GABA concentration significantly elevated in the ipsilateral substantia nigra. At that time, apomorphine (1–8 mg kg −1 ) and (+) amphetamine (1–8 mg kg −1 ) injected intraperitoneally produced dose-dependent turning of the rats towards the injected side. There was a close temporal relationship between the increase in GABA concentration in the substantia nigra (an increase which was confined to the substantia nigra and which persisted for up to 10 days) and apomorphine-induced turning. No such behavioural changes were produced by EOS injected into the mesencephalic reticular formation or saline injections into the substantia nigra. After unilateral electrolytic lesions in the substantia nigra, similar doses of apomorphine and amphetamine produced turning towards the lesioned side and the response could still be elicited 48 days after lesioning. The dopamine concentration was reduced and the homovanillic acid concentration was increased significantly in the ipsilateral striatum 24 hr after EOS pretreatment and 14 days after electrolytic lesioning. Both dopamine and homovanillic acid concentrations returned to control levels seven days after EOS pretreatment. There was a significant increase in the firing rate of spontaneously active zona compacta neurones in the ipsilateral substantia nigra, 24 hr after EOS injection. It is concluded that the elevation of GABA concentration in the zona reticulata of the substantia nigra, or electrolytic lesions in this area, indirectly increased the activity of the ipsilateral nigro-striatal dopaminergic system. A tentative hypothesis is proposed to explain these observations.