A common profile of prefrontal cortical activation following exposure to nicotine- or chocolate-associated contextual cues

Neuroscience. 2001;105(3):535-45. doi: 10.1016/s0306-4522(01)00221-4.


Conditioning and learning factors are likely to play key roles in the process of addiction and in relapse to drug use. In nicotine addiction, for example, contextual cues associated with smoking can be powerful determinants of craving and relapse, even after considerable periods of abstinence. Using the detection of the immediate-early gene product, Fos, we examined which regions of the brain are activated by environmental cues associated with nicotine administration, and compared this profile to the pattern induced by cues associated with a natural reward, chocolate. In the first experiment, rats were treated with either nicotine (0.4 mg/ml/kg) or saline once per day for 10 days in a test environment distinct from their home cages. In the second experiment, rats were given access to either a bowl of chocolate chips or an empty bowl in the distinct environment for 10 days. After a 4-day interval, rats were re-introduced to the environment where they previously received either nicotine treatment or chocolate access. Nicotine-associated sensory cues elicited marked and specific activation of Fos expression in prefrontal cortical and limbic regions. Moreover, exposure to cues associated with the natural reward, chocolate, induced a pattern of gene expression that showed many similarities with that elicited by drug cues, particularly in prefrontal regions. These observations support the hypothesis that addictive drugs induce long-term neuroadaptations in brain regions subserving normal learning and memory for motivationally salient stimuli.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Behavior, Animal / drug effects
  • Behavior, Animal / physiology
  • Cacao
  • Candy
  • Cell Count
  • Conditioning, Psychological / drug effects*
  • Conditioning, Psychological / physiology
  • Cues*
  • Learning / drug effects*
  • Learning / physiology
  • Male
  • Motor Activity / drug effects
  • Motor Activity / physiology
  • Neural Pathways / drug effects
  • Neural Pathways / metabolism
  • Neuronal Plasticity / drug effects
  • Neuronal Plasticity / physiology
  • Neurons / drug effects
  • Neurons / metabolism
  • Nicotine / pharmacology*
  • Prefrontal Cortex / drug effects*
  • Prefrontal Cortex / metabolism
  • Proto-Oncogene Proteins c-fos / metabolism
  • Rats
  • Rats, Sprague-Dawley
  • Recurrence
  • Reward*
  • Tobacco Use Disorder / metabolism*
  • Tobacco Use Disorder / physiopathology


  • Proto-Oncogene Proteins c-fos
  • Nicotine