Correlation between the discharge rate of non-dopamine neurons in substantia nigra and ventral tegmental area and the motor activity induced by apomorphine

Abstract

The effects of systemic apomorphine on the discharge rates of non-dopamine neurons of the ventral tegmental area and the substantia nigra were investigated in the behaving rat to determine the relationship between the neural responses and the motor activity induced by the dopamine agonist. Apomorphine, 3.0 mg/kg, induced large increases in motor activity and in the rate of firing of non-dopamine neurons in both ventral tegmental area and substantia nigra. The effects were similar in both structures, but only a portion of the non-dopamine neurons sampled were sensitive to the dopamine agonist. The motor and unit responses were correlated for latencies, magnitude and duration. These effects were dose-responsive, 0.75 mg/kg and 1.5 mg/kg inducing smaller behavioral and neural responses than 3.0 mg/kg. Apomorphine, 3.0 mg/kg, given to rats pretreated with haloperidol, 1.5 mg/kg, 60 min before the recording session, induced smaller behavioral and neural responses than in controls. The dopamine agonist given to rats in which gross motor activity was prevented through light anesthesia with urethan, 600 mg/kg, led to a decrease in the magnitude of the unit response in ventral tegmental area, and to a potentiation of the response in substantia nigra. In rats with bilateral electrolytic lesions of nucleus accumbens given one week earlier, apomorphine induced a smaller behavioral response than in controls, and differential effects on the neural responses. In ventral tegmental area the response was the same as in controls, but in substantia nigra it was blocked. These results indicate the presence in substantia nigra and ventral tegmental area of subpopulations of non-dopamine neurons responding with excitation to experimental manipulations that activate dopamine receptors. The dissociation between the motor effects of apomorphine and the neural effects in the subjects prevented from expressing gross motor activity, and in the lesioned animals, indicates that the neural responses were not the result of behavioral feedback. And the differential effects of apomorphine in ventral tegmental area and substantia nigra in these two groups of subjects suggest that the dopamine motor influence, at this brain level, may be fractionated, different groups of non-dopamine neurons conveying different aspects of the dopamine influence on motor activity to premotor neurons. The results, taken together, support the notion that non-dopamine efferent neurons in ventral tegmental area and substantia nigra function as dopamine output neurons, their output being critical for the behavioral effects of dopamine agonists.