Amperozide, a Novel Antipsychotic Drug, Inhibits the Ability of d‐Amphetamine to Increase Dopamine Release In Vivo in Rat Striatum and Nucleus Accumbens

Abstract: The in vivo effects of amperozide, a novel atypical antipsychotic drug, on the release of dopamine (DA) and the output of its metabolite, 3,4‐dihydroxyphenylacetic acid (DOPAC), were investigated in the striatum and the nucleus accumbens of awake, freely moving rats using microdialysis. Amperozide (2–10 mg/kg, s.c.) significantly increased extracellular levels of DA in both the striatum and nucleus accumbens in a dose‐dependent manner. It had a similar but lesser effect on extracellular DOPAC levels in both regions. d‐Amphetamine (2 mg/kg, s.c.) alone produced a very large (43‐fold) increase in DA release, together with a 70% decrease in DOPAC levels in both the striatum and the nucleus accumbens. Amperozide (1–5 mg/kg, s.c.) 30 min before d‐amphetamine (2 mg/kg) dose‐dependently attenuated d‐amphetamine‐induced DA release but had no effect on the ‐amphetamine‐induced decrease in extracellular DOPAC levels in both regions. The effect of amperozide on d‐amphetamine‐induced DA release in the nucleus accumbens may explain the inhibitory effect of amperozide on amphetamine‐induced locomotor activity. However, the failure of amperozide to block amphetamine‐induced stereotypy, despite marked inhibition of striatal DA release, suggests the need to reexamine the importance of striatal DA for amphetamine‐induced stereotypy.