Persistent catalepsy associated with severe dyskinesias in rats treated with chronic injections of haloperidol decanoate.
Patients who develop persistent parkinsonism while on chronic neuroleptic therapy may be predisposed towards the development of tardive dyskinesia (TD). We investigated this issue in an animal model of TD by examining the association between catalepsy and the syndrome of neuroleptic-induced vacuous chewing movements (VCMs). VCMs were measured every 3 weeks for 33 weeks while rats received injections of haloperidol decanoate. Catalepsy was measured after the second through the seventh injections of the depot neuroleptic. There were no correlations between the severity of catalepsy scores after the second or third injections of haloperidol and the severity of the overall VCM syndrome. However, the severity of the catalepsy score following the third through seventh injections of haloperidol strongly correlated with the concurrent number of VCMs. Persistent high catalepsy scores across the six catalepsy rating sessions were strongly associated with the development of persistent severe VCMs. These findings suggest that, to the extent that persistent parkinsonian signs in humans are associated with a propensity towards the development of TD, the VCM syndrome in rats is at least a partially faithful animal model of this relationship.
Hyde
T M
TM
Clinical Brain Disorders Branch, National Institute of Mental Health, St. Elizabeths Hospital, Washington, DC 20032, USA.
Egan
M F
MF
Wing
L L
LL
Wyatt
R J
RJ
Weinberger
D R
DR
Kleinman
J E
JE
D000818:Animals; D014150:Antipsychotic Agents / Q000009:adverse effects* / Q000494:pharmacology; D002375:Catalepsy / Q000139:chemically induced*; D004195:Disease Models, Animal; D004409:Dyskinesia, Drug-Induced / Q000209:etiology; D006220:Haloperidol / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000494:pharmacology; D008297:Male; D010302:Parkinson Disease, Secondary / Q000139:chemically induced*; D051381:Rats; D017207:Rats, Sprague-Dawley
D014150:Antipsychotic Agents; C033563:haloperidol decanoate; D006220:Haloperidol