Efficacy of the atypical antipsychotic aripiprazole in d-amphetamine-based preclinical models of mania.
The atypical antipsychotic aripiprazole has been demonstrated to reduce symptoms of bipolar mania. To further profile the antimanic-like properties of aripiprazole in relevant preclinical models, we examined its efficacy in d-amphetamine-based behavioural models of acute mania in rats. The effects of acute and repeated administration of aripiprazole were assessed in the facilitation of intracranial self-stimulation (ICSS) and hyperlocomotion after acute d-amphetamine, and in the sensitized facilitation of ICSS function and hyperlocomotion after repeated d-amphetamine. Acutely, aripiprazole (0.75, 1.5 and 2.5 mg/kg i.p.) increased ICSS thresholds, attenuated the reward-facilitating effects of d-amphetamine (0.5 mg/kg i.p.), decreased motor activity and prevented d-amphetamine-induced hyperlocomotion. Co-administration of aripiprazole and d-amphetamine for 7 d resulted in aripiprazole counteracting the d-amphetamine-induced sensitization in facilitation of brain reward function and hyperlocomotion. These results indicate the efficacy of aripiprazole in d-amphetamine-based preclinical models of acute mania that are characterized by increased motivational drive and/or hyperfunction of brain reward.
Mavrikaki
Maria
M
Laboratory of Behavioral Neuroscience, Department of Psychology, School of Social Sciences, University of Crete, Rethymno, Crete, Greece.
Nomikos
George G
GG
Panagis
George
G
D000818:Animals; D014150:Antipsychotic Agents / Q000008:administration & dosage / Q000494:pharmacology; D000068180:Aripiprazole; D001714:Bipolar Disorder / Q000139:chemically induced* / Q000188:drug therapy*; D000697:Central Nervous System Stimulants / Q000008:administration & dosage / Q000037:antagonists & inhibitors / Q000494:pharmacology; D003913:Dextroamphetamine / Q000008:administration & dosage / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D008124:Locomotion / Q000187:drug effects; D008297:Male; D010879:Piperazines / Q000008:administration & dosage / Q000494:pharmacology*; D015363:Quinolones / Q000008:administration & dosage / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012653:Self Stimulation / Q000187:drug effects*
D014150:Antipsychotic Agents; D000697:Central Nervous System Stimulants; D010879:Piperazines; D015363:Quinolones; D000068180:Aripiprazole; D003913:Dextroamphetamine