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Psychopharmacology (Berl). 2008 Jun;198(2):181-90. doi: 10.1007/s00213-008-1115-x. Epub 2008 Apr 3.

Interactions between age and the aversive effects of nicotine withdrawal under mecamylamine-precipitated and spontaneous conditions in male Wistar rats.

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Department of Neuroscience, Centre for Addiction and Mental Health, 33 Russell Street, T700, Toronto, ON, Canada M5S 2S1.



Adolescent onset of smoking is associated with a rapid progression to dependence. Although adolescents may exhibit a greater susceptibility to nicotine addiction, relatively little is known about the influence of the aversive effects of nicotine withdrawal in maintaining smoking behavior.


The present study investigated age differences in the motivational effects of mecamylamine-precipitated and spontaneous nicotine withdrawal in adolescent and adult rats using the conditioned place aversion procedure (CPA).


In experiment 1, adolescent (postnatal day (PD) 28) and adult (PD60) male Wistar rats chronically treated with nicotine (3 or 6 mg/kg/day, s.c.) received mecamylamine (1 mg/kg, s.c.), a nicotinic receptor antagonist, or vehicle prior to place conditioning; physical withdrawal signs were also measured. Experiment 2 was conducted to increase nicotine levels in which adolescents were treated with 4.5 or 9 mg/kg/day nicotine. In experiment 3, age differences in spontaneous nicotine withdrawal were evaluated.


Nicotine-treated adults developed a CPA to the mecamylamine-associated compartment and expressed significant physical withdrawal signs, whereas similarly treated adolescents did not. Increasing nicotine exposure levels did not modify the adolescent response to mecamylamine-precipitated withdrawal. Spontaneous nicotine withdrawal produced similar physical withdrawal signs in adolescents and adults, but did not elicit CPA.


The current study indicates that adolescent rats are less responsive to the aversive effects of mecamylamine-precipitated, but not spontaneous, nicotine withdrawal compared to adult rats. These findings suggest that adolescents and adults may exhibit similar sensitivity to the affective and physical effects of withdrawal following smoking cessation.

[Indexed for MEDLINE]

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