Difference in catalepsy response in inbred rats during chronic haloperidol treatment is not predictive of the intensity of behavioral hypersensitivity which subsequently develops.
An animal model was utilized to explore the observed clinical association between a history of significant neuroleptic-induced parkinsonism and an increased incidence for the subsequent development of tardive dyskinesia. Catalepsy-sensitive Fisher rats and catalepsy-resistant Brown Norway rats were treated for 14 days with haloperidol at a dose of either 1 mg/kg or 5 mg/kg daily. Following a 7-day drug withdrawal period, rats were tested for behavioral hypersensitivity to acute challenge with apomorphine and then striata were assayed for 3H-spiroperidol receptor binding. Despite significant interstrain difference in catalepsy response to either neuroleptic dose, Brown Norway rats treated with 5 mg/kg developed behavioral hypersensitivity and D-2 receptor supersensitivity equivalent to that of the similarly treated Fisher rats. Catalepsy, a possible rat analog for neuroleptic-induced parkinsonism, therefore did not predict the intensity of those subsequent behavioral and receptor changes considered to result from chronic antagonism of striatal dopamine receptors and to possibly underlie tardive dyskinesia. Further studies are required to elucidate the less than obvious relationship between extrapyramidal behavioral effects of chronic neuroleptic treatment.
Kinon
B J
BJ
Psychiatric Research Department, Hillside Hospital, Glen Oaks, NY 11004.
Kane
J M
JM
D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D002375:Catalepsy / Q000139:chemically induced* / Q000523:psychology; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism; D006220:Haloperidol / Q000494:pharmacology*; D008297:Male; D051381:Rats; D011916:Rats, Inbred F344; D011954:Receptors, Dopamine / Q000378:metabolism; D013045:Species Specificity; D013134:Spiperone; D013239:Stereotyped Behavior / Q000187:drug effects
D011954:Receptors, Dopamine; D013134:Spiperone; D006220:Haloperidol