Nicotine self-administration and withdrawal: modulation of anxiety in the social interaction test in rats

Psychopharmacology (Berl). 2001 Jan;153(3):315-20. doi: 10.1007/s002130000586.


Rationale: Most smokers report smoking has an anxiolytic effect, which may contribute to nicotine dependence.

Objective: To examine effects in the social interaction test (SI) of anxiety after 4 weeks' self-administered nicotine (15 infusions of 0.03 mg/kg, totalling 0.45 mg/kg per day), and after 24 and 72 h of withdrawal. The effect of exposure to the operant chamber on withdrawal responses was also examined.

Methods: Animals were trained to self-administer saline or nicotine and after 4 weeks they were tested in SI after their daily self-administration session. Animals were retested after 24 and 72 h withdrawal, when they were either taken directly from the home cage or were tested 5 min after a 30-min exposure to the operant chamber.

Results: Compared with the saline control group, the animals that had been self-administering nicotine for 4 weeks showed decreased social interaction with no decrease in locomotor activity, indicating a significant anxiogenic effect of the nicotine infusions. There was no change in social interaction after 24 and 72 h withdrawal from chronic nicotine, regardless of whether or not the rats were exposed to the operant chamber just prior to being tested.

Conclusions: Nicotine self-administration is not maintained because of its anxiolytic effect, but despite, or because of, its anxiogenic effect. There was no evidence of an anxiogenic response after either 24 or 72 h of withdrawal and thus increased anxiety on withdrawal from nicotine does not seem to contribute to nicotine self-administration.

MeSH terms

  • Animals
  • Anxiety / chemically induced*
  • Anxiety / psychology
  • Conditioning, Operant / drug effects*
  • Conditioning, Operant / physiology
  • Male
  • Motor Activity / drug effects*
  • Motor Activity / physiology
  • Nicotine / administration & dosage
  • Nicotine / pharmacology*
  • Nicotinic Agonists / administration & dosage
  • Nicotinic Agonists / pharmacology*
  • Rats
  • Rats, Wistar
  • Self Administration / psychology
  • Social Behavior
  • Substance Withdrawal Syndrome* / psychology


  • Nicotinic Agonists
  • Nicotine