An animal model to study the molecular basis of tardive dyskinesia.
Long-term treatment with haloperidol is associated with a number of extrapyramidal side effects. This limitation presents a marked therapeutic challenge. The present method (21 days administration of haloperidol, 5 mg/kg, i.p.) has been established to gain deeper insight into the molecular etiology (inflammation and apoptosis) of haloperidol-induced cellular death. In the present model, besides the corresponding increase in the vacuous chewing movements (VCMs), enhanced oxidative stress, there was a significant increase in cellular markers of inflammation and apoptotic protein (caspase-3), leading to cellular death. We also suggest that this model will be effective in preclinical testing of new chemical entities for the treatment of haloperidol induced tardive dyskinesia and related symptoms.
Department of Pharmacology, Southern Illinois University School of Medicine, Springfield, IL, USA. mbishnoi@siumed.edu
Mahendra
M
Bishnoi
Ravneet K
RK
Boparai
D000818:Animals; D014150:Antipsychotic Agents / Q000009:adverse effects / Q000378:metabolism / Q000627:therapeutic use; D017209:Apoptosis; D001522:Behavior, Animal / Q000187:drug effects; D053148:Caspase 3 / Q000378:metabolism; D003024:Clozapine / Q000008:administration & dosage; D004195:Disease Models, Animal; D004409:Dyskinesia, Drug-Induced / Q000188:drug therapy* / Q000378:metabolism*; D006220:Haloperidol / Q000009:adverse effects* / Q000627:therapeutic use*; D006801:Humans; D008297:Male; D009069:Movement Disorders / Q000378:metabolism*; D011281:Pregnatrienes / Q000008:administration & dosage; D051381:Rats; D017208:Rats, Wistar
D014150:Antipsychotic Agents; D011281:Pregnatrienes; D053148:Caspase 3; C053356:U 74500A; D003024:Clozapine; D006220:Haloperidol