Decrease in the evoked release of endogenous dopamine and dihydroxyphenylacetic acid from rat striatal slices after withdrawal from repeated haloperidol.

Abstract

The release of endogenous DA (dopamine) and DOPAC (3,4-dihydroxyphenylacetic acid) from rat striatal slices was measured after withdrawal from a prior long-term treatment of the rat with haloperidol to investigate adaptive changes in striatal DA and DOPAC release induced by chronic haloperidol treatment. Striatal slices prepared 24 h after the last injection of daily treatment with haloperidol for up to 14 days (2.5 mg/kg per day) were superfused and stimulated for 5 min with K+ (50 mM). Haloperidol treatment for 3 or 7 days decreased K(+)-stimulated DA release by maximally 35%, but a 14-day treatment was not effective. The K(+)-stimulated release of DOPAC, which occurred after the change in DA release, was reduced significantly by the treatment for 7 or 14 days. A higher daily dose of haloperidol (10 mg/kg per day) produced a more pronounced decrease in stimulated DA release after a 14-day treatment without having an effect after 3 days. However, the stimulated release of DOPAC decreased markedly after both 3 and 14 days of haloperidol treatment. The slight reduction in the DA content of the slices after K+ stimulation was seen in some haloperidol-treated tissues, although this change did not always parallel the simultaneous decrease in DA release. These results indicate that the K(+)-induced stimulation of endogenous DA release and the synthesis of DA are impaired after withdrawal from repeated haloperidol treatment.