Autoradiographic and pharmacological studies on the role of dopamine D3 receptors in genetically dystonic ( dtsz) hamsters

Abstract

Previous examinations demonstrated periodic increases in striatal extracellular dopamine levels during dystonic attacks and changes in dopamine D1 and D2 receptor binding in the dt sz mutant hamster, an animal model of paroxysmal non-kinesiogenic dyskinesia in which dystonic episodes can be induced by stress. Since dopamine D3 receptors are involved in the regulation of striatal dopamine release, D3 receptor function was investigated by autoradiographic and pharmacological examinations in mutant hamsters in the present study. [ 125I]7-[[(E)-3-iodoprop-2-enyl]-propylamino]-5,6,7,8-tetrahydronaphthalen-2-ol ([ 125I]7-OH-PIPAT) binding was not significantly altered in the striatum, n. accumbens, ventral pallidum or cerebellum in dt sz hamsters in comparison to non-dystonic control hamsters. In line with the unaltered D3 receptor binding, the preferential dopamine D3 versus D2 receptor antagonist U-99194 (5,6-dimethoxy- N, N-dipropyl-2,3-dihydro-1H-inden-2-amine hydrochloride) did not exert significant effects on the severity of dystonia in dt sz hamsters at doses of 10 to 40 mg/kg which induced hyperlocomotion. These results suggest that periodic elevations of dopamine levels in these animals are not related to D3 receptor dysfunctions.