Decreased catalepsy response to haloperidol in the genetically dystonic (dt) rat

Abstract

The rat mutantdystonic displays an autosomal recessive neurological disease characterized by slow, twisting movements of the limbs and trunk. Rats displaying clinical signs also show a decreased behavioral response to the dopaminergic blocker, haloperidol. Investigation of the development of the cataleptic response to haloperidol in the dystonic (dt) rat indicated that the response of thedt rat in the bar test is similar to that of normal littermates until after the appearance of clinical symptoms in the mutants on postnatal day 10. Mutant rats did not differ from their normal littermates in responses to another cataleptic agent, morphine. Assessment of the integrity of the nigrostriatal dopamine (DA) system did not indicate the presence of any degenerative process or of any alterations in DA metabolism. No reliable differences were found between normal anddt rats in striatal DA levels or turnover rates; in DA levels in response to γ-hydroxybutyrolactone; or in the number and affinity of striatal DA or muscarinic acetylcholine receptors. Nor did qualitative light microscopic examination of Golgi-impregnated tissue fromdt rats indicate the presence of any morphological abnormalities in the striatum. These findings suggest that dystonic symptoms can occur in the absence of an alteration in striatal DA metabolism and that thedt rat may have a defect in a pathway efferent to the stritum.