A role of the polysynaptic system of substantia nigra in the cholinergic-dopaminergic equilibrium in the central nervous system

Summary Unilateral intranigral injections of apomorphine (APO, 2 g) depressed locomotor activity and increased relax EEG pattern in the rabbit, while carbachol (Carb, 2 g) increased the locomotor activity, elevated the alert index, and produced episodes of epileptoidal discharges, usually beginning in the substantia nigra (SN). They were most intensive in the VL thalamic and weaker in the caudate nucleus. Carb also produced sniffing, head turning and rotations ipsilateral to the injection side. APO given into the same site 15 min before Carb abolished or decreased the intensity of EEG epileptoidal discharges, antagonized sniffing and prevented rotations. Given into SN, APO depressed the homovanillic acid (HVA) level in both striata, the effect being highly significant only in the ipsilateral structure. Carb also depressed weakly the striatal HVA level. The HVA level in rabbits receiving a combined treatment (APO 15 min before Carb) did not differ from that in solvent-injected animals.The results suggest that (i) dopamine-sensitive receptors in SN exert an inhibitory influence on the activity of dopamine nerve endings in the striatum, (ii) cholinergic stimulation of SN produces a complex effect on the striatal dopamine nerve ending activity, as it is most probably mediated through two different cholinoceptive outputs from SN: through the nigrostriatal pathway and the nigrothalamic pathway, (iii) simultaneous stimulation of dopamine and acetylocholine receptors in SN shows that the final effects of these two systems are mutually antagonistic and that, (iv) SN may play an important role in balancing the activity of bilateral striata.Preliminary data were presented to the German Pharmacological Society Meeting at Hannover, September 1976