Journal
NEUROPHARMACOLOGY
Volume 57, Issue 1, Pages 60-66Publisher
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.neuropharm.2009.04.006
Keywords
Nicotine; Varenicline; Dopamine; alpha 4 beta 2 receptors; Reward; Addiction
Categories
Funding
- Intramural Research Program of the National Institute on Drug Abuse (NIDA)
- National Institutes of Health (NIH), U.S.A
Ask authors/readers for more resources
Varenicline, a partial alpha 4 beta 2 and full alpha 7 nicotinic receptor agonist, has been shown to inhibit nicotine self-administration and nicotine-induced increases in extracellular dopamine in the nucleus accumbens. In the present study, we investigated whether varenicline inhibits nicotine-enhanced electrical brain-stimulation reward (BSR), and if so, which receptor subtypes are involved. Systemic administration of nicotine (0.25-1.0 mg/kg, i.p.) or varenicline (0.03-3 mg/kg, i.p.) produced biphasic effects, with low doses producing enhancement (e.g., decreased BSR threshold), and high doses inhibiting BSR. Pretreatment with low dose (0.03-1.0 mg/kg) varenicline dose-dependently attenuated nicotine (0.25 or 0.5 mg/kg)-enhanced BSR. The BSR-enhancing effect produced by varenicline was blocked by mecamylamine (a high affinity nicotinic receptor antagonist) or dihydro-erythroicline (a relatively selective nicotinic alpha 4-containing receptor antagonist), but not methyllycaconitine (a selective alpha 7 receptor antagonist), suggesting an effect mediated by activation of alpha 4 beta 2 receptors. This suggestion is supported by findings that the alpha 4 beta 2 receptor agonist SIB-1765F produced a dose-dependent enhancement of BSR, while pretreatment with SIB-1765F attenuated nicotine (0.5 mg/kg)-enhanced BSR. In contrast, the selective alpha 7 receptor agonist ARR-17779, altered neither BSR itself nor nicotine-enhanced BSR, at any dose tested. These findings suggest that: 1) varenicline inhibits nicotine-enhanced BSR, supporting its use as a smoking cessation aid; and 2) varenicline-enhanced BSR by itself and varenicline's anti-nicotine effects are mediated by activation of alpha 4 beta 2, but not alpha 7, receptors. Published by Elsevier Ltd.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available