Aripiprazole, an atypical antipsychotic, prevents the motor hyperactivity induced by psychotomimetics and psychostimulants in mice.
Aripiprazole is an atypical antipsychotic that acts as a partial agonist at the dopamine D(2) receptor. It has been mainly investigated in dopamine-based models of schizophrenia, while its effects on glutamate-based paradigms have remained to be further characterized. Due to its unique mechanism of action, aripiprazole has also been considered as a replacement medication for psychostimulant abuse. Thus, in the present study we tested the hypothesis that aripiprazole would prevent the motor hyperactivity induced by psychostimulant and psychotomimetic drugs that act either by dopaminergic or glutamatergic mechanisms. Male Swiss mice received injections of aripiprazole (0.1-1 mg/kg) followed by drugs that enhance the dopamine-mediated neurotransmission, amphetamine (3 mg/kg) or cocaine (5 mg/kg), or by glutamate NMDA-receptor antagonists, ketamine (60 mg/kg) or MK-801 (0.4 mg/kg). Independent groups also received aripiprazole (0.1-1 mg/kg) or haloperidol (0.5 mg/kg) and were tested for catalepsy. All doses of aripiprazole were effective in preventing the motor stimulant effects of amphetamine and cocaine. Moreover, the higher dose also prevented the effects of ketamine and MK-801. The present study reports the effects of aripiprazole in dopaminergic and glutamatergic models predictive of antipsychotic activity, suggesting that both may be useful for screening novel partial agonists with antipsychotic activity. It also shows that aripiprazole may prevent the acute effects of psychostimulant drugs without significant motor impairment.
Leite
Juliana V
JV
Department of Pharmacology, Ribeirão Preto School of Medicine, University of São Paulo Av. Bandeirantes 3900, Ribeirão Preto-SP, 14049-900, Brazil.
Guimarães
Francisco S
FS
Moreira
Fabricio A
FA
D000661:Amphetamine / Q000633:toxicity; D000818:Animals; D014150:Antipsychotic Agents / Q000494:pharmacology* / Q000633:toxicity; D000068180:Aripiprazole; D002375:Catalepsy / Q000139:chemically induced; D000697:Central Nervous System Stimulants / Q000633:toxicity*; D003042:Cocaine / Q000633:toxicity; D016291:Dizocilpine Maleate / Q000633:toxicity; D004298:Dopamine / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004353:Drug Evaluation, Preclinical / Q000379:methods; D054333:Drug Partial Agonism; D018691:Excitatory Amino Acid Antagonists / Q000633:toxicity*; D005973:Glutamine / Q000378:metabolism; D006220:Haloperidol / Q000494:pharmacology; D006948:Hyperkinesis / Q000139:chemically induced / Q000378:metabolism / Q000503:physiopathology / Q000517:prevention & control*; D007649:Ketamine / Q000633:toxicity; D008124:Locomotion / Q000187:drug effects; D008297:Male; D051379:Mice; D009043:Motor Activity / Q000187:drug effects*; D010879:Piperazines / Q000494:pharmacology* / Q000633:toxicity; D015363:Quinolones / Q000494:pharmacology* / Q000633:toxicity; D017448:Receptors, Dopamine D2 / Q000187:drug effects / Q000378:metabolism; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors / Q000378:metabolism; D013997:Time Factors
D014150:Antipsychotic Agents; D000697:Central Nervous System Stimulants; D018691:Excitatory Amino Acid Antagonists; D010879:Piperazines; D015363:Quinolones; D017448:Receptors, Dopamine D2; D016194:Receptors, N-Methyl-D-Aspartate; D005973:Glutamine; D007649:Ketamine; D016291:Dizocilpine Maleate; D000068180:Aripiprazole; D000661:Amphetamine; D003042:Cocaine; D006220:Haloperidol; D004298:Dopamine