MARKED REGIONAL DISTURBANCES IN BRAIN METABOLISM OF MONOAMINERGIC NEUROTRANSMITTERS IN THE GENETICALLY DYSTONIC HAMSTER

The genetically dystonic hamster is an animal model of idiopathic (tor sion) dystonia that displays sustained abnormal movements and postures either spontaneously or in response to mild environmental stimuli. Si nce dystonic attacks occur in the absence of any lesion which can be d efined by standard histopathological techniques in the central nervous system, the presumption is that dystonia in mutant hamsters is due to some biochemical disturbance activity in brain regions involved in mo tor functions. In the present study we determined the monoamine neurot ransmitters dopamine, noradrenaline, adrenaline and serotonin (5-HT) a s well as the dopamine metabolites homovanillic acid (HVA) and dihydro xyphenylacetic acid (DOPAC) and the 5-HT metabolite 5-hydroxyindoleace tic acid (5-HIAA) in 14 brain regions of male and female dystonic hams ters and age-matched non-dystonic controls. All determinations were do ne at age of maximum susceptibility for induction of dystonic attacks. Since both genders of dystonic hamsters exhibit the same characterist ic age-dependent time-course of dystonia, it was assumed that only tho se biochemical alterations are critically involved in dystonia that oc cur in both female and male animals. The neurochemical data show that except for a significant decrease of dopamine and HVA in the olfactory bulb, no consistent changes in dopamine metabolism are present across brain regions, including the basal ganglia, of dystonic hamsters. In contrast, marked increases in noradrenaline and 5-HT or 5-HIAA were fo und in several brain areas of both genders, indicating an enhanced act ivity of central noradrenergic and serotonergic nuclei in the brainste m. The present results suggest the involvement of noradrenergic and se rotonergic neural systems in the pathophysiology of dystonia. Based on these data and recent theoretical suggestions from clinical findings, drugs which reduce noradrenergic and serotonergic neurotransmission m ay be a useful therapeutic approach to dystonia.