Phencyclidine-induced rotational behavior in rats with nigrostriatal lesions and its modulation by dopaminergic and cholinergic agents.

ABSTRACT

The peripheral administration of the psychotomimetic drug phencyclidine (1-(phenylcyclohexyl) piperidine hydrochloride) (PCP) induces a dose-related ipsilateral rotation in unilateral substantia nigra electrolytically-lesioned rats. The intensity of this rotation can be modulated by administration of various dopaminergic and cholinergic agents. Injection of alpha-methylparatyrosine methylester (125 mg/kg) or haloperidol (1 mg/kg) inhibited the ipsilateral circling behavior. Pimozide (1 mg/kg) also inhibitied the rotation, but to a lesser extent. The injection of the anticholinergic agent trihexyphenidyl (5 mg/kg) potentiated, and the cholinomimetic drug arecoline (5 mg/kg), depressed the rotation induced by PCP (7.5 mg/kg), It is probable that PCP possesses significant dopaminergic and anticholinergic properties. The capacity of PCP to induce rotation in this model may be related to its effects on dopaminergic and cholingergic neurons in the rat striatum. Thus, PCP may induce rotational behavior by potentiating dopaminergic transmission, by blocking cholinergic activity, or both; both of these effects have been demonstrated to be important in the generation of circling behavior in rats with nigrostriatal lesions.