Is antagonism of alpha3beta4 nicotinic receptors a strategy to reduce morphine dependence?
18-Methoxycoronaridine, a synthetic iboga alkaloid congener, has been previously shown to attenuate several signs of morphine withdrawal in rats. The recently discovered action of 18-methoxycoronaridine to block alpha3beta4 nicotinic receptors may be responsible for this effect. To test this hypothesis the effects of non-selective alpha3beta4 receptor antagonists, dextromethorphan, mecamylamine, bupropion, and their combinations, were assessed on of acute naltrexone-precipitated (1 mg/kg i.p.) morphine withdrawal in rats. Dextromethorphan (5-40 mg/kg, s.c.), mecamylamine (0.25-4 mg/kg, i.p.) and bupropion (10-30 mg/kg, i.p.) alone produced variable effects on signs of withdrawal. However, two low-dose combinations, i.e., dextromethorphan (5 mg/kg, s.c.) and mecamylamine (0.25 mg/kg, i.p.), mecamylamine (0.25 mg/kg, i.p.) and bupropion (10 mg/kg, i.p.) as well as the three-drug combination significantly attenuated diarrhea and weight loss; none of the agents administered alone had these effects. The results of the present study provide evidence that alpha3beta4 nicotinic receptors are involved in the expression of at least two signs of opioid withdrawal.
Taraschenko
Olga D
OD
Center for Neuropharmacology and Neuroscience MC-136, Albany Medical College, 47 New Scotland Avenue, Albany, NY 12208, USA. tarasco@mail.amc.edu
Panchal
Vishal
V
Maisonneuve
Isabelle M
IM
Glick
Stanley D
SD
D000208:Acute Disease; D000818:Animals; D016642:Bupropion / Q000494:pharmacology / Q000627:therapeutic use; D003915:Dextromethorphan / Q000494:pharmacology / Q000627:therapeutic use; D004359:Drug Therapy, Combination; D005260:Female; D008464:Mecamylamine / Q000494:pharmacology / Q000627:therapeutic use; D009021:Morphine Dependence / Q000503:physiopathology*; D018733:Nicotinic Antagonists / Q000494:pharmacology* / Q000627:therapeutic use; D051381:Rats; D017207:Rats, Sprague-Dawley; D011978:Receptors, Nicotinic / Q000187:drug effects*; D013375:Substance Withdrawal Syndrome / Q000378:metabolism* / Q000503:physiopathology / Q000517:prevention & control
D018733:Nicotinic Antagonists; D011978:Receptors, Nicotinic; C403530:nicotinic receptor alpha3beta4; D016642:Bupropion; D008464:Mecamylamine; D003915:Dextromethorphan