Suppression of dopamine-related side effects of morphine by aripiprazole, a dopamine system stabilizer

• Published in: European journal of pharmacology Vol. 600; no. 1; pp. 105 - 109
• Main Authors: Narita, Minoru, Takei, Daisuke, Shiokawa, Mitsuru, Tsurukawa, Yuri, Matsushima, Yuki, Nakamura, Atsushi, Takagi, Shigemi, Asato, Megumi, Ikegami, Daigo, Narita, Michiko, Amano, Taku, Niikura, Keiichi, Hashimoto, Keisuke, Kuzumaki, Naoko, Suzuki, Tsutomu
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier B.V 14.12.2008; Elsevier
• Subjects: Analgesics, Opioid - adverse effects; Animals; Antipsychotic Agents - administration & dosage; Antipsychotic Agents - adverse effects; Antipsychotic Agents - pharmacology; Aripiprazole; Biological and medical sciences; Catalepsy - chemically induced; Dependence; Dopamine; Dopamine - metabolism; Dopamine Antagonists - administration & dosage; Dopamine Antagonists - adverse effects; Dopamine Antagonists - pharmacology; Dose-Response Relationship, Drug; Hyperkinesis - chemically induced; Male; Medical sciences; Mice; Mice, Inbred ICR; Morphine; Morphine - adverse effects; Nucleus Accumbens - drug effects; Nucleus Accumbens - metabolism; Opioid; Pharmacology. Drug treatments; Piperazines - administration & dosage; Piperazines - adverse effects; Piperazines - pharmacology; Prochlorperazine - administration & dosage; Prochlorperazine - adverse effects; Prochlorperazine - pharmacology; Quinolones - administration & dosage; Quinolones - adverse effects; Quinolones - pharmacology; Reward; Severity of Illness Index; Opioid; Morphine; Dopamine; Aripiprazole; Dependence; 5-HT2A serotonin receptor; Partial agonist; Atypical antipsychotic; Neuroleptic; Psychotropic; Toxicity; Quinolinone derivatives; Opiates; Catecholamine; Narcotic analgesic; Opioid peptide; D2 Dopamine receptor; 5-HT1A Serotonine receptor; Neurotransmitter; Antagonist
• ISSN: 0014-2999; 1879-0712
• DOI: 10.1016/j.ejphar.2008.10.030

Dopamine receptor antagonists are commonly used to counter the adverse effects of opioids such as hallucinations, delusions and emesis. However, most of these agents themselves have side effects, including extrapyramidal symptoms. Here, we investigated the effect of the dopamine system stabilizer aripiprazole on morphine-induced dopamine-related actions in mice. Morphine-induced hyperlocomotion and reward were significantly suppressed by either the dopamine receptor antagonist prochlorperazine or aripiprazole. Catalepsy was observed with a high dose of prochlorperazine, but not with an even higher dose of aripiprazole. The increased level of dialysate dopamine in the nucleus accumbens stimulated by morphine was significantly decreased by pretreatment with aripiprazole. These results suggest that the co-administration of aripiprazole may be useful for reducing the severity of morphine-induced dopamine-related side effects.