Differential effects of acute and chronic haloperidol treatment on striatal and nigral 3, 4-dihydroxyphenylacetic acid (DOPAC) levels

Chronic treatment of rats with haloperidol (4 weeks, 0.5 or 1 mg/kg) resulted in a significant attenuation of the large DOPAC rise seen in the corpus striatum after acute treatment. This tolerance effect was observed both shortly following termination of chronic treatment and on challenge with a low dose (0.1 mg/kg) of the drug 6–8 days later. In contrast, acute haloperidol treatment resulted in only a small and nonsignificant elevation of DOPAC levels in the substantia nigra, while chronic treatment caused a larger and significant increase in levels of the metabolite. Moreover, the latter effect was also observed in response to haloperidol challenge 6–8 days after discontinuation of drug treatment. The differential pattern of response in these two brain regions is discussed in relation to possible mechanisms mediating striatal tolerance and to recent observations regarding changes in nigral dopamine cell firing after chronic haloperidol treatment.