Striatal dopamine metabolism increases during long-term haloperidol administration in rats but shows tolerance in response to acute challenge with raclopride.

The release and metabolism of dopamine (DA) in the striatum of rats during long-term haloperidol administration (32 weeks) was assessed using in vivo microdialysis. Basal levels of homovanillic acid (HVA) and dihydroxyphenylacetic acid (DOPAC) were significantly elevated over control values, while basal DA release was not significantly increased. The specific DA D2 receptor antagonist, raclopride (0.5 mg/kg, i.p.), increased DA release and metabolism in control animals, but this effect was profoundly blocked in the haloperidol treated group. These results suggest that chronic haloperidol treatment may induce compensatory increases in basal DA activity even though response to an acute D2 antagonist shows significant tolerance.