Effects of antipsychotic drugs on the long-term effects of amphetamine on nigro-striatal dopamine neurons in iprindole-treated rats.

Abstract

The decrease in striatal dopamine (DA) at 1 week after the administration of a single injection of (+)-amphetamine sulfate (9.2 mg/kg) to iprindole-treated (10 mg/kg of iprindole hydrochloride) rats was prevented by haloperidol (0.2 mg/kg), sulpiride (32 mg/kg), pimozide (2 mg/kg), chlorpromazine hydrochloride (3.5 mg/kg), fluphenazine 2-hydrochloride (0.25 mg/kg) and (+)-butaclamol hydrochloride (1 mg/kg) but not by (-)-butaclamol hydrochloride (1 mg/kg) or clozapine (40 mg/kg). The same dose of sulpiride did not significantly attenuate the rotational behavior induced by the administration of (+)-amphetamine sulfate (9.2 mg/kg) to iprindole-treated rats with unilateral aspiration lesions of the striatum. The concentration of amphetamine in the brains of iprindole-treated rats at 8 h after (+)-amphetamine sulfate (9.2 mg/kg) administration was not altered by the coadministration of haloperidol (1 mg/kg), sulpiride (32 mg/kg), pimozide (2 mg/kg) or clozapine (40 mg/kg). Recovery of striatal DA after depletion by alpha-methyl-m-tyrosine (alpha MMT) (50 mg/kg) was facilitated by haloperidol (0.2 mg/kg) and sulpiride (32 mg/kg) but not by clozapine (40 mg/kg). The possibility that neuroleptic drugs antagonize both the short-term depletion of striatal DA produced by alpha MMT and the long-term depletion of striatal DA produced by amphetamine in iprindole-treated rats by an effect on the nerve impulse-mediated release of vesicular transmitter is discussed.