title: Repeated administration of nicotine attenuates the development of morphine tolerance and dependence in mice.
abstract: Clinical use of morphine in pain management is a controversial issue. Both nicotine and morphine are widely abused. So, investigating the interaction between nicotinic and opioid receptors is of great interest to both basic mechanistic and clinical view. We investigated the influence of repeated administration of nicotine on the development of morphine tolerance and dependence. Adult male albino mice were rendered dependent on morphine by subcutaneous (s.c.) injections three times daily for 3 days. Repeated intraperitoneal (i.p.) injection of nicotine (0.001-2 mg/kg) or saline (1 ml/kg) was performed 15 min prior to each morphine injection. Maximal possible effect (MPE%) of morphine (50 mg/kg; s.c.) was used on the fourth day as an index for the development of tolerance. Likewise, to assess the occurrence of dependence in drug-treated mice, naloxone (5 mg/kg; i.p.) was injected 2 h after the last dose of morphine. Repeated nicotine administration significantly attenuated the development of tolerance in a dose-dependent manner whereas it significantly decreased withdrawal jumping behavior in a biphasic profile (V-shape) manner. Furthermore, the central nicotinic receptor antagonist mecamylamine (0.01-0.1 mg/kg; i.p.) neither the peripheral nicotinic receptor antagonist hexamethonium (0.01 and 0.1 mg/kg; i.p.) nor the muscarinic receptor antagonist atropine (2.5-10 mg/kg; i.p.), dose-dependently antagonized both the inhibition of withdrawal jumping as well as increase in MPE% which was produced by repeated nicotine administration (0.1 mg/kg; i.p.). On the other hand, 3 days of solely nicotine treatment resulted in significant jumping behavior precipitated by naloxone after single morphine injection on the test day. The data suggests that the inhibitory effect of nicotine on the morphine tolerance and dependence is mediated by central nicotinic receptors and there is a cross-dependence between nicotine and morphine.
authors.affiliation: Neuroscience Research Center, Shaheed Beheshti Medical University, P.O.Box 19615-1178, Tehran, Iran. Haghparast@yahoo.com
authors.forename: Abbas
authors.initials: A
authors.lastname: Haghparast
authors.forename: Abbas
authors.initials: A
authors.lastname: Khani
authors.forename: Nima
authors.initials: N
authors.lastname: Naderi
authors.forename: Amir-Mohammad
authors.initials: AM
authors.lastname: Alizadeh
authors.forename: Fereshteh
authors.initials: F
authors.lastname: Motamedi
mesh_terms: D000701:Analgesics, Opioid / Q000494:pharmacology*; D000818:Animals; D001285:Atropine / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004361:Drug Tolerance; D005730:Ganglionic Blockers / Q000494:pharmacology; D006584:Hexamethonium Compounds / Q000494:pharmacology; D008297:Male; D008464:Mecamylamine / Q000494:pharmacology; D051379:Mice; D009020:Morphine / Q000494:pharmacology*; D009021:Morphine Dependence / Q000517:prevention & control*; D018727:Muscarinic Antagonists / Q000494:pharmacology; D009270:Naloxone / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000494:pharmacology; D009538:Nicotine / Q000494:pharmacology*; D018722:Nicotinic Agonists / Q000494:pharmacology*; D018733:Nicotinic Antagonists / Q000494:pharmacology; D010147:Pain Measurement / Q000187:drug effects; D013375:Substance Withdrawal Syndrome / Q000523:psychology
chemical_list: D000701:Analgesics, Opioid; D005730:Ganglionic Blockers; D006584:Hexamethonium Compounds; D018727:Muscarinic Antagonists; D009292:Narcotic Antagonists; D018722:Nicotinic Agonists; D018733:Nicotinic Antagonists; D009270:Naloxone; D008464:Mecamylamine; D009538:Nicotine; D009020:Morphine; D001285:Atropine