The pathophysiology of various types of
dyskinesias, including dystonias, is poorly understood. Clinical and epidemiological studies in humans revealed that the severity of
dyskinesias and the frequency of paroxysmal forms of the disease are altered by factors such as the onset of puberty, pregnancy, cyclical changes and stress, indicating an underlying hormonal component. The dystonic phenotype in the dt(sz) hamster, a genetic animal model of
paroxysmal dystonia, has been suggested to be based on a deficit of striatal
gamma-aminobutyric acid (
GABA)ergic interneurons and changes in the
GABA(A) receptor complex. In this animal model, hormonal influences seem to be also involved in the pathophysiology, but an influence of peripheral
sex hormones has already been excluded. Possibly,
neurosteroids as endogenous regulators of the
GABA(A) receptor may be critically involved in the pathophysiology of
dystonia in this animal model. Therefore, in the present study, the effects of the
neurosteroids allopregnanolone acetate and
allotetrahydrodeoxycorticosterone (
THDOC), representing positive modulators of the
GABA(A) receptor, as well as of the negative
GABA(A) receptor modulators
pregnenolone sulfate and
dehydroepiandrosterone (
DHEA), on severity of
dystonia were examined in dt(sz) hamsters after acute
intraperitoneal injections.
Allopregnanolone acetate and
THDOC exerted a moderate reduction of
dystonia, whereas
pregnenolone sulfate and
DHEA had no significant effects. Although the effects of
allopregnanolone acetate and
THDOC were moderate and short-lasting, the present results suggest that changes in
neurosteroid levels might be involved in the initiation of dystonic episodes. Future studies have to include measurements of brain
neurosteroid levels as well as of chronic
neurosteroid administrations to clarify the pathophysiological role and therapeutic potential of
neurosteroids in
dystonia.