title: The antipsychotic aripiprazole selectively prevents the stimulant and rewarding effects of morphine in mice.
abstract: Aripiprazole is an antipsychotic that acts as a partial agonist at dopamine D2 receptors, with a favorable pharmacological profile. Due to its unique mechanism of action, this compound has potential application as a substitutive therapy for drug addiction. Considering that distinct neural systems subserve the addictive and analgesic actions of opioids, we tested the hypothesis that aripiprazole selectively inhibit the abuse-related, but not the antinociceptive, effects of morphine. The drugs were tested in male Swiss mice for their effects on locomotion, conditioned place preference (CPP) and nociception. Morphine (20mg/kg) increased motor activity, whereas aripiprazole (0.1, 1 and 10mg/kg) did not induce any change. This antipsychotic, however, prevented morphine-induced locomotion. In the conditioning box, aripiprazole did not induce either reward or aversion. Yet, it prevented both the acquisition and the expression of morphine-induced CPP. Finally, none of the doses of this antipsychotic interfere with morphine (5mg/kg)-induced antinociception in the tail-flick test. In conclusion, aripiprazole inhibited the abuse-related effects of morphine at doses that do not interfere with basal locomotion, reward or aversion. Also, it did not alter morphine-induced antinociceptive effects. This antipsychotic should be further investigated as a possible substitutive strategy for treating certain aspects of opioid addiction.
authors.affiliation: Department of Pharmacology, Institute of Biological Sciences, Universidade Federal de Minas Gerais, Av. Antônio Carlos 6627, 31270-901 Belo Horizonte, MG, Brazil.
authors.forename: Ana F
authors.initials: AF
authors.lastname: Almeida-Santos
authors.affiliation: Department of Pharmacology, Institute of Biological Sciences, Universidade Federal de Minas Gerais, Av. Antônio Carlos 6627, 31270-901 Belo Horizonte, MG, Brazil.
authors.forename: Pedro H
authors.initials: PH
authors.lastname: Gobira
authors.affiliation: Department of Pharmacology, Institute of Biological Sciences, Universidade Federal de Minas Gerais, Av. Antônio Carlos 6627, 31270-901 Belo Horizonte, MG, Brazil.
authors.forename: Diego P
authors.initials: DP
authors.lastname: Souza
authors.affiliation: Department of Pharmacology, Institute of Biological Sciences, Universidade Federal de Minas Gerais, Av. Antônio Carlos 6627, 31270-901 Belo Horizonte, MG, Brazil.
authors.forename: Renata C M
authors.initials: RC
authors.lastname: Ferreira
authors.affiliation: Department of Pharmacology, Institute of Biological Sciences, Universidade Federal de Minas Gerais, Av. Antônio Carlos 6627, 31270-901 Belo Horizonte, MG, Brazil.
authors.forename: Thiago R
authors.initials: TR
authors.lastname: Romero
authors.affiliation: Department of Pharmacology, Institute of Biological Sciences, Universidade Federal de Minas Gerais, Av. Antônio Carlos 6627, 31270-901 Belo Horizonte, MG, Brazil.
authors.forename: Igor D
authors.initials: ID
authors.lastname: Duarte
authors.affiliation: Department of Pharmacology, Institute of Biological Sciences, Universidade Federal de Minas Gerais, Av. Antônio Carlos 6627, 31270-901 Belo Horizonte, MG, Brazil.
authors.forename: Daniele C
authors.initials: DC
authors.lastname: Aguiar
authors.affiliation: Department of Pharmacology, Institute of Biological Sciences, Universidade Federal de Minas Gerais, Av. Antônio Carlos 6627, 31270-901 Belo Horizonte, MG, Brazil. Electronic address: fabriciomoreira@icb.ufmg.br.
authors.forename: Fabricio A
authors.initials: FA
authors.lastname: Moreira
mesh_terms: D000818:Animals; D014150:Antipsychotic Agents / Q000008:administration & dosage / Q000494:pharmacology*; D000068180:Aripiprazole; D000697:Central Nervous System Stimulants / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D003213:Conditioning, Psychological / Q000187:drug effects; D004195:Disease Models, Animal; D008297:Male; D051379:Mice; D009020:Morphine / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D009043:Motor Activity / Q000187:drug effects; D059225:Nociception / Q000187:drug effects; D009293:Opioid-Related Disorders / Q000188:drug therapy / Q000503:physiopathology / Q000523:psychology; D010879:Piperazines / Q000008:administration & dosage / Q000494:pharmacology*; D015363:Quinolones / Q000008:administration & dosage / Q000494:pharmacology*; D012201:Reward
chemical_list: D014150:Antipsychotic Agents; D000697:Central Nervous System Stimulants; D010879:Piperazines; D015363:Quinolones; D009020:Morphine; D000068180:Aripiprazole
keywords: Abuse; Addiction; Antipsychotic; Aripiprazole; Conditioned place preference; Morphine