Subconvulsive dose of pentylenetetrazole increases the firing rate of substantia nigra pars reticulata neurons in dystonic but not in nondystonic hamsters.

Abstract

Dystonic attacks, including twisting movements, can be initiated by mild stress in mutant (gene symbol dt(sz)) Syrian golden hamsters, an animal model of idiopathic paroxysmal dystonia. Previous studies suggested that dysfunctions in basal ganglia, which are not restricted to periods of attacks, are involved in the dystonic syndrome in mutant hamsters. Therefore, in the present study in anesthetized animals, we examined whether the spontaneous firing rate of extracellularly recorded neurons of the substantia nigra pars reticulata (SNr) differs between dt(sz) and age-matched nondystonic control hamsters. Furthermore, we investigated the responsiveness of these nondopaminergic, presumably GABAergic neurons to a subconvulsive dose (25mg/kg i.p.) of systemically applied pentylenetetrazole (PTZ), which exerts prodystonic effects in mutant hamsters. The mean basal (spontaneous) firing rate of SNr neurons was not altered in mutant hamsters. However, within 5 min after i.p. injection of PTZ, the mean firing rate of SNr neurons significantly increased to about 160% of predrug control values in dt(sz) but not in control hamsters. Although the present study failed to reveal changes in the basal firing rate of SNr neurons in mutant hamsters, the abnormal response to PTZ is in line with previous pharmacological and biochemical data indicating disturbed function of the GABAergic system.