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: M-R Zarrindast, H Homayoun, S Khavandgar, M Fayaz-Dastgerdi, M Fayaz-Dastgerdi
• Journal: Behavioural pharmacology (Behav Pharmacol) Vol. 13 Issue 2 Pg. 117-25 (Mar 2002) ISSN: 0955-8810 [Print] England
• PMID: 11981224 (Publication Type: Journal Article)

Chemical References

• Adrenergic alpha-2 Receptor Agonists
• Adrenergic alpha-2 Receptor Antagonists
• Adrenergic alpha-Agonists
• Adrenergic alpha-Antagonists
• Enzyme Inhibitors
• Narcotic Antagonists
• Yohimbine
• Naloxone
• Arginine
• Nitric Oxide Synthase
• Nitric Oxide Synthase Type I
• Nos1 protein, mouse
• Clonidine
• NG-Nitroarginine Methyl Ester

Topics

• Adrenergic alpha-2 Receptor Agonists
• Adrenergic alpha-2 Receptor Antagonists
• Adrenergic alpha-Agonists (pharmacology)
• Adrenergic alpha-Antagonists (pharmacology)
• Animals
• Arginine (pharmacology)
• Clonidine (pharmacology)
• Enzyme Inhibitors (pharmacology)
• Male
• Mice
• Morphine Dependence (psychology)
• NG-Nitroarginine Methyl Ester (pharmacology)
• Naloxone (pharmacology)
• Narcotic Antagonists (pharmacology)
• Nitric Oxide Synthase (antagonists & inhibitors)
• Nitric Oxide Synthase Type I
• Substance Withdrawal Syndrome (psychology)
• Yohimbine (pharmacology)