Amperozide, a novel antipsychotic drug, inhibits the ability of d-amphetamine to increase dopamine release in vivo in rat striatum and nucleus accumbens.
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 d-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.
Ichikawa
J
J
Department of Psychiatry and Pharmacology, Case Western Reserve University School of Medicine, Cleveland, Ohio.
Meltzer
H Y
HY
D015102:3,4-Dihydroxyphenylacetic Acid / Q000032:analysis / Q000378:metabolism; D000662:Amphetamines / Q000494:pharmacology*; D000818:Animals; D014150:Antipsychotic Agents / Q000494:pharmacology*; D002851:Chromatography, High Pressure Liquid; D003342:Corpus Striatum / Q000737:chemistry / Q000378:metabolism*; D004298:Dopamine / Q000032:analysis / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D008297:Male; D009714:Nucleus Accumbens / Q000737:chemistry / Q000378:metabolism*; D010879:Piperazines / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D013997:Time Factors
D000662:Amphetamines; D014150:Antipsychotic Agents; D010879:Piperazines; C049058:amperozide; D015102:3,4-Dihydroxyphenylacetic Acid; D004298:Dopamine