Age-dependent alterations in reward-seeking behavior after brief nicotine exposure

Psychopharmacology (Berl). 2014 Apr;231(8):1763-73. doi: 10.1007/s00213-013-3266-7. Epub 2013 Sep 13.


Rationale: Adolescence is a developmental period that coincides with the onset of tobacco use. Teen smokers are also more likely to abuse other drugs compared to nonsmokers. Previous studies with rats have shown that low-dose nicotine pretreatment enhances initial acquisition of cocaine self-administration when given during early adolescence, but not at later ages. The aim of the present study was to determine whether these nicotine pretreatment effects extend to extinction and reinstatement of reward-seeking behavior.

Methods: Adolescent [postnatal day (P)28] and adult rats (P86) were pretreated for 4 days with nicotine (60 μg/kg, i.v.) or saline. Following pretreatment, rats were allowed to nose poke for cocaine (500 μg/kg/infusion) or sucrose pellets for at least 12 days or until meeting acquisition criterion. Responding was then extinguished for at least 7 days or until extinction criterion was met. The following day, the rats were reinstated with either a priming injection of cocaine (10 mg/kg, i.p.) or sucrose pellets.

Results: Nicotine markedly enhanced extinction of cocaine self-administration in adolescent rats, but not adults. Pretreatment also enhanced the acquisition of cocaine self-administration in adolescents, while reducing discrimination for the reinforced hole in adults. There were no pretreatment or age effects on cocaine-induced reinstatement. In contrast, nicotine induced only minor enhancement of sucrose-taking behavior in adolescents, with no significant impact on extinction or reinstatement at either age.

Conclusions: Nicotine pretreatment affects reward-related behavior in both an age- and reward-dependent manner. These findings show that brief nicotine exposure during early adolescence enhances drug-related learning.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Aging / drug effects*
  • Aging / physiology
  • Animals
  • Appetitive Behavior / drug effects*
  • Appetitive Behavior / physiology
  • Catheters, Indwelling
  • Cocaine / administration & dosage
  • Conditioning, Operant
  • Dietary Sucrose / administration & dosage
  • Dopamine Uptake Inhibitors / administration & dosage
  • Drug-Seeking Behavior / drug effects
  • Drug-Seeking Behavior / physiology
  • Extinction, Psychological / drug effects
  • Extinction, Psychological / physiology
  • Male
  • Nicotine / pharmacology*
  • Nicotinic Agonists / pharmacology*
  • Rats, Sprague-Dawley
  • Reward*
  • Self Administration


  • Dietary Sucrose
  • Dopamine Uptake Inhibitors
  • Nicotinic Agonists
  • Nicotine
  • Cocaine