Sensitization of neuronal response to cocaine during withdrawal following chronic treatment

Neuroreport. 1996 Aug 12;7(12):2041-5. doi: 10.1097/00001756-199608120-00038.


The neural basis of sensitization was examined by assessing the expression of zif/268 mRNA in cortical and striatal neurons following cocaine challenge (30 mg kg-1, i.p.) after 2 weeks of daily treatment with cocaine or saline vehicle. Acute cocaine challenge induced zif/268 mRNA expression in neurons of the caudate putamen (CP), nucleus accumbens (NAc) shell and prelimbic cortex. Chronic cocaine treatment attenuated zif/268 mRNA expression in these regions, although zif/268 mRNA response in CP neurons recovered after 7 days of withdrawal. In contrast, cocaine challenge during withdrawal augmented zif/268 response in neurons of the infralimbic cortex and olfactory tubercle. Sensitized activity in these regions could serve to amplify mesolimbic dopamine and NAc responses, and might provide a critical stimulus to drug craving.

Publication types

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

MeSH terms

  • Animals
  • Autoradiography
  • Cerebral Cortex / drug effects*
  • Cocaine / pharmacology*
  • DNA-Binding Proteins / drug effects*
  • Early Growth Response Protein 1
  • Immediate-Early Proteins*
  • Male
  • RNA, Messenger / metabolism
  • Rats
  • Rats, Sprague-Dawley
  • Sensitivity and Specificity
  • Substance Withdrawal Syndrome / metabolism*
  • Time Factors
  • Transcription Factors / drug effects*


  • DNA-Binding Proteins
  • Early Growth Response Protein 1
  • Egr1 protein, rat
  • Immediate-Early Proteins
  • RNA, Messenger
  • Transcription Factors
  • Cocaine