Research PapersThe effects of simultaneous administration of α2-adrenergic agents with L-NAME or L-arginine on the development and expression of morphine dependence in miceZarrindast, M.-R.; Homayoun, H.; Khavandgar, S.; Fayaz-Dastgerdi, M. Author Information Department of Pharmacology, School of Medicine, Tehran University of Medical Sciences, PO Box 13145-784, Tehran, Iran Correspondence to M.-R. Zarrindast, Department of Pharmacology, School of Medicine, Tehran University of Medical Sciences, PO Box 13145-784, Tehran, Iran. E-mail: [email protected] Received 9 October 2001 accepted as revised 4 January 2002 Behavioural Pharmacology: March 2002 - Volume 13 - Issue 2 - p 117-125 Buy Abstract Both α2-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 α2-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, α2-adrenergic and NO pathways seem to be functionally linked in the modulation of opioid dependence. © 2002 Lippincott Williams & Wilkins, Inc.