Varenicline and mecamylamine attenuate locomotor sensitization and cross-sensitization induced by nicotine and morphine in mice.
The present study focused on the evaluation of behavioural sensitization and cross-sensitization induced by nicotine and morphine in mice. First, we revealed that after 9days of nicotine administration (0.175mg/kg, free base), every other day and following its 7-day withdrawal, challenge doses of nicotine (0.175mg/kg) and morphine (5mg/kg) induced locomotor sensitization in mice. When we examined the influence of varenicline, a partial alpha4beta2 nicotinic receptor agonist (0.5, 1 and 2mg/kg) and mecamylamine (0.5, 1 and 2mg/kg), a non-selective nicotinic receptor antagonist, we found that both agents attenuated the acquisition and expression of nicotine sensitization as well as locomotor cross-sensitization between nicotine and morphine. Our results indicate similar cholinergic mechanisms involved in the locomotor stimulant effects of nicotine and morphine in mice, and as such these data may suggest that nicotinic neurotransmission could be a potential target for developing pharmacotherapeutic strategies to treat and prevent nicotine and/or opioid addiction.
Biala
Grazyna
G
Department of Pharmacology and Pharmacodynamics, Medical University of Lublin, 4 Staszica Street, 20-081 Lublin, Poland. grazyna.biala@umlub.pl
Staniak
Natasza
N
D000701:Analgesics, Opioid / Q000494:pharmacology; D000818:Animals; D001552:Benzazepines / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D008297:Male; D008464:Mecamylamine / Q000494:pharmacology*; D051379:Mice; D009020:Morphine / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D009043:Motor Activity / Q000187:drug effects*; D009538:Nicotine / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D018722:Nicotinic Agonists / Q000494:pharmacology*; D018733:Nicotinic Antagonists / Q000494:pharmacology; D011810:Quinoxalines / Q000494:pharmacology*; D000068580:Varenicline
D000701:Analgesics, Opioid; D001552:Benzazepines; D018722:Nicotinic Agonists; D018733:Nicotinic Antagonists; D011810:Quinoxalines; D008464:Mecamylamine; D009538:Nicotine; D009020:Morphine; D000068580:Varenicline