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.