Article

Mecamylamine attenuates cue-induced reinstatement of nicotine-seeking behavior in rats.

Department of Psychology, University of Pittsburgh, Pittsburgh, PA 15260, USA.
Neuropsychopharmacology (impact factor: 7.99). 04/2007; 32(3):710-8. DOI:10.1038/sj.npp.1301129 pp.710-8
Source: PubMed

ABSTRACT Mecamylamine, a noncompetitive nicotinic cholinergic antagonist, inhibits nicotine self-administration in animals and may attenuate tobacco smoking in humans trying to quit. Our preliminary data suggested that this agent, at a dose of 2 mg/kg (subcutaneous (s.c.)), also attenuates cue-induced relapse to nicotine-seeking behavior in rats. This study determined whether mecamylamine-induced attenuation can be obtained at doses lower than the high 2 mg/kg dose used in the first study, and whether it is specific to nicotine-associated cues. Male Sprague-Dawley rats were trained to intravenously self-administer nicotine (0.03 mg/kg/infusion) on a fixed-ratio 5 schedule. Each infusion was accompanied by a visual cue (1 s onset of a lever light followed by offset of a house light for 20 s during which time no infusions could be obtained). After the nicotine-maintained responding was extinguished by withholding the delivery of nicotine (saline substitution) and its associated cue, reinstatement tests were conducted. Response-contingent re-presentation of the cue without further availability of nicotine significantly reinstated extinguished responding at the previously nicotine-reinforced lever. Pretreatment with mecamylamine (0.5, 1, and 2 mg/kg, s.c.) dose-dependently attenuated the cue-induced reinstatement of lever responding. Mecamylamine did not change food-taking and -seeking responses, whereas the highest dose (2 mg/kg) decreased nicotine self-administration behavior. The results confirm previous findings that stimuli conditioned to nicotine self-administration effectively elicit reinstatement of nicotine-seeking behavior after extinction and demonstrate that mecamylamine, besides suppressing self-administration of nicotine, effectively attenuates cue-induced nicotine-seeking behavior. These findings suggest that the response-reinstatement procedures used in this study may be useful for studying neurobiological mechanisms of nicotine-seeking behavior and that mecamylamine-like drugs may be potential candidates for pharmacological treatment and prevention of relapse to tobacco smoking in abstinent smokers.

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Keywords

-seeking responses
 
1 s onset
 
2 mg/kg dose
 
abstinent smokers
 
attenuates cue-induced nicotine-seeking behavior
 
attenuates cue-induced relapse
 
fixed-ratio 5 schedule
 
house light
 
inhibits nicotine self-administration
 
intravenously self-administer nicotine
 
lever light
 
Male Sprague-Dawley rats
 
mecamylamine-like drugs
 
nicotine self-administration
 
nicotine self-administration behavior
 
nicotine-associated cues
 
nicotine-reinforced lever
 
noncompetitive nicotinic cholinergic antagonist
 
suppressing self-administration
 
tobacco smoking