The muscarine antagonist methscopolamine and the NMDA antagonist AP-5 injected unilaterally into the nucleus accumbens cause mice to rotate in opposite directions.

Abstract

Previously, we have reported that the NMDA antagonist AP-5, injected unilaterally into the nucleus accumbens of mice, induces ipsilateral rotation in monoaminergically intact mice, but contralateral rotation in monoamine-depleted animals. In this paper we report that the muscarine antagonist methscopolamine, injected unilaterally into the nucleus accumbens, induced predominantly contralateral rotation in monoaminergically intact mice. In monoamine-depleted animals intra-accumbens methscopolamine induced only a weak stimulation of rotational behaviour (not significant), but the direction of the rotation was exclusively contralateral, and the animals showed contralateral body deviation. Moreover, when these animals received additional treatment with the alpha-adrenergic agonist clonidine, which potentiates the motor effects of cholinergic antagonists in monoamine-depleted mice (Carlsson et al., 1991), a clear-cut contralateral rotation was induced. The observed behavioural effects are discussed in relation to the positive and negative feedback circuits, which link the nucleus accumbens with the cerebral cortex and thalamus. In previous papers, we have suggested that the ipsilateral rotation induced by AP-5 is mediated primarily by the positive feedback circuit, whereas the AP-5-induced contralateral rotation is due to interference with primarily the negative feedback circuit. Applying this reasoning to the rotational effects of methscopolamine, it seems that methscopolamine interferes primarily with the negative feedback circuit.