Time-dependent changes in cocaine-seeking behavior and extracellular dopamine levels in the amygdala during cocaine withdrawal

Neuropsychopharmacology. 1998 Jul;19(1):48-59. doi: 10.1016/S0893-133X(97)00205-4.


Cocaine and cocaine-associated cues elicit craving in addicts and reinstate cocaine-seeking behavior in rats. Craving and cocaine-seeking behavior may be mediated by withdrawal-induced changes in dopamine (DA) neurotransmission in the amygdala. To examine whether there are concomittant changes in cocaine-seeking behavior and extracellular DA levels during withdrawal, experimental rats were trained to self-administer cocaine (0.75 mg/kg i.v.). After 14 daily 3-hour training sessions, animals underwent either a 1-day, 1-week, or 1-month withdrawal period. Extracellular DA levels were assessed during baseline, extinction, cue reinstatement, and cocaine (15 mg/kg i.p.) reinstatement of cocaine-seeking behavior (i.e., defined as the difference in nonreinforced lever presses on an active minus inactive lever). Cocaine-seeking behavior became more intense during the course of cocaine withdrawal. Additionally, basal and cocaine-induced extracellular DA levels were enhanced after the 1-month withdrawal period. We suggest that the former may reflect a persistent elevation in tonic extracellular DA levels in the amygdala, whereas the latter may reflect a persistent elevation in phasic extracellular DA levels.

Publication types

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

MeSH terms

  • Amygdala / drug effects*
  • Amygdala / metabolism
  • Amygdala / ultrastructure
  • Animals
  • Cocaine / administration & dosage
  • Cocaine / toxicity*
  • Cocaine-Related Disorders / physiopathology*
  • Cues
  • Dopamine / metabolism*
  • Extracellular Space / metabolism
  • Male
  • Microdialysis
  • Rats
  • Rats, Sprague-Dawley
  • Self Administration
  • Substance Withdrawal Syndrome / metabolism*
  • Substance Withdrawal Syndrome / physiopathology*


  • Cocaine
  • Dopamine