A low dose of nicotine is sufficient to produce nicotine withdrawal in mice

Abstract

The objective of our study was to investigate whether the chronic administration of a low dose of nicotine can be followed by a withdrawal syndrome at cessation of nicotine delivery. Pre-vious studies showed various results, depend-ing in the doses of nicotine, species, ways of administration and behavioural paradigms, but all emphasized a withdrawal effect on some or all of the following spontaneous behaviours: grooming, rearing, body shake or tremor, body scratching, abdominal constriction, jumping. However, it is not clear which behaviour is ex-actly altered, as a global behavioural index is most frequently used. This is not clear either if anxiety modulates the behavioral expression of withdrawal or which factors contribute to its locomotors effect, if any. To distant-angle these processes, we scored each of these behaviours individually before nicotine exposure, during continuous nicotine delivery and at cessation of nicotine delivery after precipitated withdrawal by mecamylamine injection. We also measured locomotor activity and anxiety levels in the same animals. We used a low dose of nicotine (2.4 mg/kg/day as free base) that has been pre-viously shown to produce nicotinic receptors up-regulation, both in the brain and in blood cells. With such a low dose, nicotine withdrawal didn’t affect locomotion nor anxiety levels but increased the number of rearing, jumping, and marginally, body-scratching. Other behaviours, classically considered to contribute to with-drawal syndrome, were unaffected, e.g., groom- ing, body or forelimb shakes. Our results show that anxiety may be dissociated from the be-havioural withdrawal syndrome. Also, the se-verity of the syndrome produced by nicotine withdrawal is qualitatively and quantitatively different from the one induced by other drugs of abuse and also by the one produced by nicotine at higher doses.