Effects of continuous administration for 12 months of amine-depleting drugs and chlorpromazine on striatal dopamine function in the rat.

Rats received either chlorpromazine (33-36 mg/kg/day), oxypertine (6.3-7.3 mg/kg/day), tetrabenazine (6.0-6.7 mg/kg/day) or reserpine (0.28-0.30 mg/kg/day) continuously for up to 12 months. Chlorpromazine and tetrabenazine reduced spontaneous locomotor activity of animals after 1 month of treatment. Thereafter, locomotor activity in animals treated with chlorpromazine returned to control levels, whereas treatment with tetrabenazine increased locomotion. Oxypertine enhanced spontaneous locomotor activity after 9 months of administration only, whereas treatment with reserpine did not alter this activity at any time during the study compared to age-matched controls. Treatment with tetrabenazine enhanced stereotyped behaviour induced by apomorphine (0.063-1.0 mg/kg s.c.) throughout the study. In contrast, stereotypy in animals administered chlorpromazine, oxypertine or reserpine was the same as in control animals throughout the 12 months of treatment. Levels of dopamine in the striatum were reduced after the first month of administration of chlorpromazine, but thereafter returned to control values. Treatment with oxypertine for up to 12 months did not alter concentrations of dopamine in the striatum, whereas administration of tetrabenazine and reserpine caused a decrease. All treatments with drugs consistently reduced the content of homovanillic acid in the striatum during the study. The Bmax for specific binding of [3H]spiperone in the striatum was increased by continuous treatment of animals with chlorpromazine, oxypertine or tetrabenazine, although the effects of oxypertine and tetrabenazine were only transient. Administration of reserpine did not alter the Bmax for specific binding of [3H]spiperone. The Bmax for specific binding of [3H]piflutixol in the striatum was unchanged by any treatment for up to 12 months.(ABSTRACT TRUNCATED AT 250 WORDS)