title: Effect of imipramine on tolerance to morphine antinociception in the formalin test.
abstract: In this study, the effect of imipramine on morphine antinociception in tolerant and non-tolerant mice in the formalin test, was investigated. Subcutaneous administration of different test doses of morphine (3, 6 and 9 mg/kg) and intraperitoneal injection of test doses of imipramine (10, 20 and 40 mg/kg) induced a dose-dependent antinociception in non-tolerant mice, both in the first and second phases of the formalin test. The combination of morphine (1 mg/kg) with imipramine (10 mg/kg) showed a potentiated response in the second phase of the test. Combination of a single dose of morphine (1.5 mg/kg) with lower doses of imipramine (2, 4 and 8 mg/kg) did not show potentiation. The antinociceptive response of either morphine or morphine plus imipramine was reduced by the opioid receptor antagonist naloxone (2 mg/ kg). In order to induce tolerance, mice were treated subcutaneously with morphine (50 mg/kg) once daily for 3 days. On day 4, the antinociceptive effect of test doses of morphine or imipramine were assessed. Tolerance to the responses of test doses of morphine (3, 6 and 9 mg/kg), but not imipramine (10, 20 and 40 mg/kg) in both phases of the test was observed. Administration of lower dose of imipramine (4 mg/kg) before the test doses of morphine (3, 6 and 9 mg/kg) was not able to alter the expression of morphine tolerance. When imipramine was used during development of tolerance, either on days 1 and 2 or on days 2 and 3, the morphine tolerance in the second phase of the test was reduced. It is concluded that opioid receptor mechanism(s) may mediate the antidepressant-induced antinociception, however, imipramine may be useful in inhibiting morphine tolerance.
authors.affiliation: Department of Pharmacology, School of Medicine, Tehran University of Medical Sciences, Iran.
authors.forename: M R
authors.initials: MR
authors.lastname: Zarrindast
authors.forename: S
authors.initials: S
authors.lastname: Shaverdian
authors.forename: M
authors.initials: M
authors.lastname: Sahebgharani
mesh_terms: D000701:Analgesics, Opioid / Q000008:administration & dosage / Q000494:pharmacology*; D000704:Analysis of Variance; D000818:Animals; D000929:Antidepressive Agents, Tricyclic / Q000494:pharmacology*; D004202:Disinfectants / Q000633:toxicity; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D004361:Drug Tolerance; D005557:Formaldehyde / Q000633:toxicity; D007099:Imipramine / Q000008:administration & dosage / Q000627:therapeutic use*; D007274:Injections, Intraperitoneal; D008297:Male; D051379:Mice; D009020:Morphine / Q000008:administration & dosage / Q000627:therapeutic use*; D009270:Naloxone / Q000494:pharmacology; D010146:Pain / Q000139:chemically induced / Q000517:prevention & control*
chemical_list: D000701:Analgesics, Opioid; D000929:Antidepressive Agents, Tricyclic; D004202:Disinfectants; D005557:Formaldehyde; D009270:Naloxone; D009020:Morphine; D007099:Imipramine