Receptor fingerprinting the circling ci2 rat mutant: Insights into brain asymmetry and motor control

Abstract

Circling behaviour of the ci2 rat mutant, a model for hyperkinetic movement disorders, is associated with an abnormal asymmetry in striatal dopaminergic activity. Since it is more likely that imbalances in several neurotransmitter systems result in the cascade of neurochemical disturbances underlying disorders involving motor dysfunctions, we measured the densities of 12 neurotransmitter receptors in the basal ganglia and vestibular nuclei of adult circling mutants ( ci2/ ci2), non-circling littermates ( ci2/+) and controls from the background strain (LEW/Ztm). In controls, the left caudate putamen (CPu) contains lower kainate and the left globus pallidus higher AMPA densities than their right counterparts. The medial vestibular nucleus of mutants ipsilateral to the preferred direction of rotation contained higher M 2 densities than the contralateral one. ci2/+ animals presented no interhemispheric differences, did not differ behaviourally from controls, but contained lower GABA A densities in the CPu, nucleus accumbens (Acb) and reticular (Rt), ventromedial (VM) and ventral posterolateral (VPL) thalamic nuclei. Mutants contained lower GABA A (CPu, Acb, Rt, VPL) but higher nicotinic (Rt, VM) densities than controls and higher GABA A (CPu, VM) densities than ci2/+ rats. Hyperactivity level of mutants was positively correlated with the adenosine A 2A receptor densities in the ipsilateral Acb, but negatively correlated with those of the ipsilateral thalamus. Concluding, ci2/ ci2 mutants show alterations in GABA A, cholinergic and A 2A receptor densities. Our data add to the hypothesis that motor disorders such as hyperkinesias cannot be explained solely by absolute functional increases or decreases in the dopaminergic system, but are due to imbalances in several neurotransmitter systems.