title: Detection of dopaminergic supersensitivity induced by neuroleptic drugs in mice.
abstract: We investigated the sensitivity of dopaminergic receptors in mice fed neuroleptic drugs. Groups of mice were fed daily doses of approximately 10% of the LD50 of haloperidol, clozapine, chlorpromazine, trifluoperazine, or thioridazine for 2, 4, or 8 weeks. Four days after withdrawal of the neuroleptics, thozalinone, a dopaminergic stimulant, was given ip at 50 mg/kg to elicit gnawing behavior. Increased gnawing behavior was seen in mice after 4 weeks of administration of haloperidol (80%), chlorpromazine (80%), trifluoperazine (100%), and thioridazine (100%) compared with control values (50%). The gnawing behavior in mice treated with clozapine was the same as that for control mice. Levels of gnawing behavior after 2 or 8 weeks of administration of the same drugs were lower than those reported above. Alcohol increased the thozalinone-elicited gnawing behavior 2 weeks after dosing with haloperidol and trifluoperazine. After 4 and 8 weeks of administration of the drugs, the locomotor activity of mice was increased from 29-113% (4 weeks) to 37-110% (8 weeks) compared with controls. The study of neuroleptic drug-induced dopaminergic supersensitivity may serve as a method for detection of tardive dyskinesia-inducing effects.
mesh_terms: D000818:Animals; D014150:Antipsychotic Agents / Q000009:adverse effects*; D004409:Dyskinesia, Drug-Induced / Q000503:physiopathology; D000431:Ethanol / Q000494:pharmacology; D006801:Humans; D008297:Male; D051379:Mice; D009043:Motor Activity / Q000187:drug effects; D011954:Receptors, Dopamine / Q000187:drug effects*; D013375:Substance Withdrawal Syndrome / Q000503:physiopathology; D013997:Time Factors
chemical_list: D014150:Antipsychotic Agents; D011954:Receptors, Dopamine; D000431:Ethanol