The effect of chronic atypical antipsychotic drugs and haloperidol on amphetamine-induced dopamine release in vivo.
The effect of chronic administration of antipsychotic drugs (21 days in drinking water followed by 3 days drug washout) on the D-amphetamine (1.0 mg/kg, s.c.)-induced increase in dopamine (DA) release in the striatum and the nucleus accumbens of awake, freely-moving rats was investigated with microdialysis. Chronic administration of haloperidol, a typical antipsychotic, (0.5 mg/kg/day), decreased basal extracellular DA release in the striatum and the nucleus accumbens but did not affect D-amphetamine-induced DA release in either region. In marked contrast, chronic administration of three atypical antipsychotic drugs: amperozide (2 mg/kg/day), clozapine (10 mg/kg/day) and melperone (2 mg/kg/day) increased basal extracellular DA and enhanced D-amphetamine-induced DA release in the striatum. In the nucleus accumbens, basal extracellular DA was decreased by chronic amperozide, unchanged by chronic clozapine and increased by chronic melperone. Most significantly, D-amphetamine-induced DA release was inhibited by chronic amperozide or clozapine, but unaffected by chronic melperone in this region. These results suggest that atypical antipsychotic drugs can alter DA release in a region specific manner. In particular, attenuation of amphetamine-like stimulation of DA release with reduced basal DA release in the nucleus accumbens could contribute to the antipsychotic action of amperozide which has a very weak affinity for D2 DA receptors.
Ichikawa
J
J
Laboratory of Biological Psychiatry, Case Western Reserve University, Cleveland, OH 44106.
Meltzer
H Y
HY
D015102:3,4-Dihydroxyphenylacetic Acid / Q000378:metabolism; D000818:Animals; D014150:Antipsychotic Agents / Q000008:administration & dosage / Q000494:pharmacology*; D003342:Corpus Striatum / Q000187:drug effects* / Q000378:metabolism; D003913:Dextroamphetamine / Q000494:pharmacology*; D003956:Dialysis; D004298:Dopamine / Q000378:metabolism*; D006220:Haloperidol / Q000494:pharmacology*; D006719:Homovanillic Acid / Q000378:metabolism; D006897:Hydroxyindoleacetic Acid / Q000378:metabolism; D008297:Male; D009714:Nucleus Accumbens / Q000187:drug effects* / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D013997:Time Factors
D014150:Antipsychotic Agents; D015102:3,4-Dihydroxyphenylacetic Acid; D006897:Hydroxyindoleacetic Acid; D006220:Haloperidol; D003913:Dextroamphetamine; D004298:Dopamine; D006719:Homovanillic Acid