Striatal increase of extracellular dopamine levels during dystonic episodes in a genetic model of paroxysmal dyskinesia

Abstract

In vivo microdialysis was used to examine the levels of dopamine, serotonin, and their metabolites dihydroxyphenylacetic acid (DOPAC), homovanillic acid (HVA), and 5-hydroxyindoleacetic acid (5-HIAA) in the striatum of dt(sz) mutant hamsters, an animal model of paroxysmal dyskinesia, in which stress can precipitate dystonic episodes. Measurements were made under three different conditions in each animal: (1) at baseline in the absence of abnormal involuntary movements, (2) during an episode of paroxysmal dystonia precipitated by handling, and (3) during the recovery (postdystonic) period. In comparison to nondystonic control hamsters, which were treated in the same manner as dystonic animals, no changes could be detected under basal conditions, although the levels of DOPAC and HVA tended to be higher in mutant hamsters. Significantly elevated striatal levels of dopamine and DOPAC became evident during the period of stress-induced dystonic attacks in mutant hamsters. During dystonic episodes, dopamine levels were approximately 6.5-fold higher (followed by a 2.5-fold increase of DOPAC) in dt(sz) hamsters than in normal controls. Before the disappearance of dystonia, the levels of dopamine returned to basal concentrations in mutant hamsters. Consistent with previous pharmacologic findings, paroxysmal dystonia in mutant hamsters is associated with temporary increases of extracellular dopamine levels in the striatum.