Immunohistochemical and neurochemical studies on nigral and striatal functions in the circling (ci) rat, a genetic animal model with spontaneous rotational behavior

Asymmetrical spontaneous turning behavior or circling phenomena are often r elated to components of the dopaminergic system, particularly to an imbalan ce of nigrostriatal function. When a rotational preference is observed, it is typically in a direction away from the brain hemisphere with higher stri atal dopaminergic transmission. We have recently described a rat mutant (ci ) with spontaneous circling behavior and other signs of functional brain as ymmetry. Neurochemical determinations showed that mutants of both genders h ave significantly lower concentrations of dopamine and dopamine metabolites in the striatum ipsilateral to the preferred direction of rotation. In the present study, we used immunohistochemical, neurochemical, and autoradiogr aphic techniques to characterize the dopaminergic abnormalities of the ci r at mutant in more detail. Age-matched non-affected controls of the same str ain were used for comparison. Immunohistochemical labeling of dopaminergic neurons and fibers in substantia nigra pars compacta, ventral tegmental are a, and striatum did not indicate any significant neurodegeneration or asymm etry that could explain the lateralization it dopamine levels in striatum o f ci rats. Neurochemical determinations substantiated that ci rats of both genders have a significant imbalance in striatal dopamine metabolism, but a similar si,significant lateralization was also seen in non-affected female controls. Comparison of dopamine, serotonin, noradrenaline and several mon oamine metabolite levels in substantia nigra, striatum, nucleus accumbens a nd frontal cortex of ci rats and controls did not disclose any marked diffe rence between affected and non-affected animals which was consistently foun d in both genders. Quantitative autoradiographic determination of binding d ensities of dopamine transporter and D-1 and D-2 receptors in several parts of the striatum and substantia nigra indicated that ci rats have a signifi cantly higher binding density of dopamine transporter and receptors than co ntrols. Taken together, ci mutant rats of both genders exhibit an asymmetry in stri atal dopamine and metabolite levels and an enhanced dopamine transporter an d receptor binding, but the link of these differences in dopaminergic param eters with the rotational behavior of the animals is not clear yet. The lac k of any significant dopaminergic cell loss in the substantia ni,ora and th e locomotor hyperactivity observed in the mutants clearly suggest that the ci rat is not suited as a model of Parkinsonism but rather constitutes a mo del of a hyperkinetic motor syndrome. (C) 1998 IBRO. Published by Elsevier Science Ltd.