Changes in dynorphin immunoreactivity but unaltered density of enkephalin immunoreactive neurons in basal ganglia nuclei of genetically dystonic hamsters.

Dystonia is regarded as a basal ganglia disorder. In the dt(sz) hamster, a genetic animal model of paroxysmal dystonia, previous studies demonstrated a reduced density of striatal GABAergic interneurons which inhibit striatal GABAergic projection neurons. Although the disinhibition of striatal GABAergic projection neurons was evidenced in the dt(sz) hamster, alterations in their density have not been elucidated so far.

Effects of pharmacological entopeduncular manipulations on idiopathic dystonia in the dt(sz) mutant hamster.

The pathophysiology of idiopathic dystonias is still unknown, but it is regarded as a basal ganglia disorder. Previous experiments in the dt(sz) hamster, a model of primary paroxysmal dystonia, demonstrated reduced discharge rates and an abnormal pattern within the entopeduncular nucleus (EPN), a basal ganglia output structure. To clarify if this is based on abnormal gamma-aminobutyric acid(GABA)ergic or glutamatergic input, microinjections into the EPN were done in mutant hamsters in the present study.

Antidystonic efficacy of gamma-aminobutyric acid uptake inhibitors in the dtsz mutant.

In the dtsz mutant hamster, a model of paroxysmal dyskinesia in which dystonic episodes occur in response to stress, previous studies suggested that retarded development of gamma-aminobutyric acid (GABA)ergic inhibition plays a critical role in the pathogenesis. In the present study, we therefore examined the effects of selective GABA uptake inhibitors on severity of dystonia in dtsz hamsters. R(-)N-(4,4-di(3-methylthien-2-yl)-but-3-enyl) nipecotic acid hydrochloride (tiagabine, 5-20 mg/kg i.