Background: We have generated high- and low-nicotine preferring (high-NP, low-NP) rat lines using voluntary oral nicotine intake as the selection criterion. After nine generations, the estimated realized heritability for high intake was 0.26. The aim of the current study is to compare how nicotine withdrawal varies between these two lines. This new analysis would help elucidate if nicotine withdrawal and intake share common genetic mechanisms.
Methods: After exposing male and female Sprague Dawley rats (F8 generation) to six weeks of nicotine exposure, nicotine was withdrawn. Somatic signs of withdrawal, locomotor activity, and weight were measured at 16 and 40h. One week after withdrawal, resumption of nicotine intake was determined.
Results: The High-NP line had higher nicotine intake before and after withdrawal than the Low-NP line. High-NP rats were more active than Low-NP rats, and locomotor activity decreased during withdrawal; this decrease was more pronounced in the High-NP line. High-NP rats gained more weight during withdrawal than Low-NP rats. Escape attempts decreased during withdrawal in all groups, but overall females demonstrated more escape attempts than males. The other somatic signs of withdrawal were higher during withdrawal compared to baseline and more pronounced in females.
Conclusions: Selection for nicotine preference affected nicotine intake, locomotion and weight, suggesting the heritability of these traits. However, despite differences in nicotine preference and intake, high-NP and low-NP rats showed similar withdrawal responses: escape attempts decreased and somatic signs increased. Withdrawal responses of females were more pronounced than males suggesting sex differences in the negative affect induced by nicotine withdrawal. The major finding of this novel analysis is showing that nicotine preference does not predict withdrawal symptoms. This finding, together with sex differences observed during withdrawal, may contribute to a better understanding of nicotine dependence and have translational value in developing more effective strategies for smoking cessation.
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