Tyrosine hydroxylase immunoreactivity and [H-3]win 35,428 binding to the dopamine transporter in a hamster model of idiopathic paroxysmal dystonia

Recent pharmacological studies and receptor analyses have suggested that do pamine neurotransmission is enhanced in mutant dystonic hamsters (dt(sz)), a model of idiopathic paroxysmal dystonia which displays attacks of general ized dystonia in response to mild stress. In order to further characterize the nature of dopamine alterations, the present study investigated possible changes in the number of dopaminergic neurons, as defined by tyrosine hydr oxylase immunohistochemistry, as well as binding to the dopamine transporte r labelled with [H-3]WIN 35,428 in dystonic hamsters. No differences in the number of tyrosine hydroxylase-immunoreactive neurons were found within th e substantia nigra and ventral tegmental area of mutant hamsters compared t o non-dystonic control hamsters. Similarly, under basal conditions, i.e. in the absence of a dystonic episode, no significant changes in [3H]WIN 35,42 8 binding were detected in dystonic brains. However, in animals killed duri ng the expression of severe dystonia, significant decreases in dopamine tra nsporter binding became evident in the nucleus accumbens and ventral tegmen tal area in comparison to controls exposed to the same external stimulation . Since stimulation tended to increase [3H]WIN 35,428 binding in control br ains, the observed decrease in the ventral tegmental area appeared to be du e primarily to the fact that binding was increased less in dystonic brains than in similarly stimulated control animals. This finding could reflect a diminished ability of the dopamine transporter to undergo adaptive changes in response to external stressful stimulation in mutant hamsters. The selective dopamine uptake inhibitor GBR 12909 (20 m g/kg) aggravated dystonia in mutant hamsters, further suggesting that acute alterations in dopamine transporter function during stimulation may be an important component of dystonia in this model. (C) 1999 IBRO. Published by Elsevier Science Ltd.