Aripiprazole Prolongs Morphine Antinociception Effect and Disrupts Acute Morphine Tolerance

Marzieh Norouzi¹, Zahra Mousavi² and Hamed Shafaroodi²

¹Herbal Medicines Research Center, Pharmaceutical Sciences Branch, Islamic Azad University, Tehran-Iran, HMRC.

²Department of Pharmacology and Toxicology, Faculty of Pharmacy, Pharmaceutical Sciences Branch, Islamic Azad University, Tehran – Iran, IAUPS.

Corresponding Author E-mail:  mosavi50@yahoo.com

Abstract: Aripiprazole is an atypical antipsychotic drug mainly characterized by partial agonist activity at dopamine D2 and serotonin-1A receptors with minimal side effects. Based on typical antipsychotic pharmacological activity, including antinociception effect and disruption opioid anti-nociceptive tolerance, Aripiprazole activity and its interaction with morphine on nociception was evaluated by tail flick and hot plate assay in the mouse. In experiment 1, mice received aripiprazole (5, 10 and 20 mg/kg IP), saline (1 ml/kg, IP) and morphine (5 mg/kg, IP) 30 minutes prior to the test. The tail flick and hot-plate methods were used for pain evaluation. In order to assess the effect of aripiprazole on morphine antinociception in experiment 2, it was administered 30 min after morphine injection and then the test was assessed. Also, in experiment 3, the effect of aripiprazole (10 and 20 mg/kg IP), on acute morphine tolerance was studied. Comparisons between the groups were carried out using the Analysis of Variance (ANOVA), and post hoc Tukey's test. P<0.05 was considered statistically significant. The results revealed that aripiprazole, at doses that had no affected themselves (10–20 mg/kg), were significantly (P<0.001) effective on prolonging the morphine antinociceptive effect by tail flick test in mice. Also Aripiprazole (20 mg/kg) significantly increased the duration of morphine antinociception effect by hot plate test, but it did not significantly influence the morphine antinociception time course at 5 and 10 mg/kg of drug. Pretreatment with aripiprazole (20 mg/kg IP) prevented the acute morphine tolerance in hotplate test. These results also suggest that aripiprazole might have therapeutic value in combination to morphine as an adjuvant analgesic. It was also shown that partial agonist properties of D₂ and 5-HT_1A as well as antagonist properties of 5-HT_2A in aripiprazole likely account for the potentiation of morphine antinociception.

Keywords: Aripiprazole; antipsychotics; antinociceptive effect; morphine; mice

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