Aripiprazole increases dopamine but not noradrenaline and serotonin levels in the mouse prefrontal cortex.
Aripiprazole, a novel atypical antipsychotic drug, can significantly increase dopamine (DA) levels in the prefrontal cortex of rats, but only at low doses below 1mg/kg. The aim of the present work was to test the effect of aripiprazole (0, 0.1, 0.3, 3 and 30 mg/kg, i.p.) on extracellular levels of monoamines in the prefrontal cortex of freely moving C57BL/6J mice. Concurrent horizontal locomotor activity was also assessed. Aripiprazole produced a significant increase in dialysate DA levels after the administration of a low dose of 0.3mg/kg. Lower (0.1 mg/kg) or higher (3 and 30 mg/kg) doses failed to affect extracellular levels of DA. In addition, none of the doses tested in the present study produced significant changes in extracellular levels of noradrenaline (NA) and serotonin (5-HT). For the sake of comparison, clozapine (0, 3 and 10 mg/kg, s.c.) was also tested under similar conditions. Clozapine produced a dose-dependent increase in both dialysate DA and NA levels without affecting extracellular 5-HT. Locomotor activity was significantly decreased by both clozapine and aripiprazole. These data further support the hypothesis that selective activation of dopaminergic neurotransmission in the prefrontal cortex may contribute to the therapeutic efficacy of aripiprazole.
Zocchi
Alessandro
A
Centre of Excellence for Drug Discovery in Psychiatry, GlaxoSmithKline Pharmaceuticals, Neuropsychopharmacology, Via A. Fleming 4, 37135 Verona, Italy. alessandro.a.zocchi@gsk.com
Fabbri
Daniela
D
Heidbreder
Christian A
CA
D000818:Animals; D014150:Antipsychotic Agents / Q000494:pharmacology; D000068180:Aripiprazole; D003024:Clozapine / Q000494:pharmacology; D004298:Dopamine / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D045604:Extracellular Fluid / Q000187:drug effects / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D017551:Microdialysis; D009043:Motor Activity / Q000187:drug effects / Q000502:physiology; D009638:Norepinephrine / Q000378:metabolism; D010879:Piperazines / Q000494:pharmacology*; D017397:Prefrontal Cortex / Q000187:drug effects* / Q000378:metabolism; D015363:Quinolones / Q000494:pharmacology*; D012701:Serotonin / Q000378:metabolism; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology; D015854:Up-Regulation / Q000187:drug effects* / Q000502:physiology
D014150:Antipsychotic Agents; D010879:Piperazines; D015363:Quinolones; D012701:Serotonin; D000068180:Aripiprazole; D003024:Clozapine; D004298:Dopamine; D009638:Norepinephrine