title: The effects of simultaneous administration of alpha(2) -adrenergic agents with L-NAME or L-arginine on the development and expression of morphine dependence in mice.
abstract: Both alpha(2)-adrenoceptors and the L-arginine/nitric oxide (NO) pathway have been implicated in the modulation of morphine dependence. This study examined the effects of simultaneous administration of the alpha(2)-adrenoceptor agonist clonidine or the antagonist yohimbine together with the NO precursor L-arginine or the NO synthase (NOS) inhibitor NG-nitro-L-arginine methyl ester (L-NAME) on the induction and expression of morphine dependence as assessed by naloxone-precipitated withdrawal jumping and diarrhoea. Male NMRI mice weighing 20-30 g were used. In the induction phase, clonidine (0.01-0.1 mg/kg) intensified and yohimbine (0.5-2 mg/kg) attenuated the degree of morphine dependence. Yohimbine reversed the effect of clonidine. L-NAME (5 and 10 mg/kg) did not affect the development of morphine dependence, but significantly potentiated the effects of both subeffective (0.01 mg/kg) and effective (0.03 mg/kg) doses of clonidine. L-Arginine did not alter morphine dependence but inhibited the effect of clonidine. The effects of yohimbine in the induction phase were attenuated by L-NAME, but were not significantly affected by L-arginine. In the expression phase, clonidine attenuated and yohimbine intensified the signs of dependence. The effect of clonidine was inhibited by yohimbine. In the expression phase, L-NAME attenuated the withdrawal syndrome at 10 mg/kg and showed potentiation with clonidine in suppressing withdrawal signs. L-Arginine did not alter morphine dependence, but at 20 mg/kg inhibited and at 100 mg/kg potentiated the attenuating effect of clonidine on the expression of withdrawal syndrome. The effect of yohimbine on the expression phase was also attenuated by L-NAME, but was not significantly affected by L-arginine. In conclusion, alpha(2)-adrenergic and NO pathways seem to be functionally linked in the modulation of opioid dependence.
authors: Department of Pharmacology, School of Medicine, Tehran University of Medical Sciences, PO Box 13145-784, Tehran, Iran. Zarinmr@ams.ac.ir
authors: M-R
authors: MR
authors: Zarrindast
authors: H
authors: H
authors: Homayoun
authors: S
authors: S
authors: Khavandgar
authors: M
authors: M
authors: Fayaz-Dastgerdi
authors: M
authors: M
authors: Fayaz-Dastgerdi
mesh_terms: D058647:Adrenergic alpha-2 Receptor Agonists; D058669:Adrenergic alpha-2 Receptor Antagonists; D000316:Adrenergic alpha-Agonists / Q000494:pharmacology; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000818:Animals; D001120:Arginine / Q000494:pharmacology*; D003000:Clonidine / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D008297:Male; D051379:Mice; D009021:Morphine Dependence / Q000523:psychology*; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology*; D009270:Naloxone / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000494:pharmacology; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors*; D052248:Nitric Oxide Synthase Type I; D013375:Substance Withdrawal Syndrome / Q000523:psychology; D015016:Yohimbine / Q000494:pharmacology
chemical_list: D058647:Adrenergic alpha-2 Receptor Agonists; D058669:Adrenergic alpha-2 Receptor Antagonists; D000316:Adrenergic alpha-Agonists; D000317:Adrenergic alpha-Antagonists; D004791:Enzyme Inhibitors; D009292:Narcotic Antagonists; D015016:Yohimbine; D009270:Naloxone; D001120:Arginine; D019001:Nitric Oxide Synthase; D052248:Nitric Oxide Synthase Type I; C496321:Nos1 protein, mouse; D003000:Clonidine; D019331:NG-Nitroarginine Methyl Ester