Quantitative autoradiography reveals regionally selective changes in dopamine D1 and D2 receptor binding in the genetically dystonic hamster.

Dystonia has been proposed to be caused by abnormal input from thalamus to premotor cortex due to altered activity of the striatum projecting by way of the globus pallidus and substantia nigra pars reticulata to the thalamus. However, in the case of idiopathic dystonia, i.e. the most common form of dystonia in humans, there is only limited evidence to support such a neuroanatomic concept. In view of the problems of studying the pathophysiology of idiopathic dystonia in patients, genetically determined animal models of idiopathic dystonia may be used as a practical means of studying brain dysfunctions involved in this movement disorder. The genetically dystonic hamster is an animal model of idiopathic dystonia that displays sustained abnormal movements and postures either spontaneously or in response to mild environmental stimuli. Autoradiographic analysis of dopamine D1 receptor density, using the ligand [3H]SCH 23390, revealed significant decreases of D1 binding in several parts of the striatum and substantia nigra pars reticulata of dystonic hamsters. Binding of the D2 ligand [3H]YM-09151-2 was decreased in the dorsomedial caudate-putamen, but increased in nucleus accumbens. In most other sites studied, no significant changes were found in either [3H]SCH 23390 or [3H]YM-09151-2 binding. By studying groups of dystonic hamsters in the absence and presence of dystonic attacks, it was shown that most changes in D1 and D2 binding were not secondary to abnormal movement but rather due to the dystonic condition of the animals. The study provides evidence of altered dopamine receptor binding in dystonia and confirms the concept that basal ganglia dysfunction may be a primary component of dystonia.