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

Ly T L Tran-Nguyen, Rita A. Fuchs, Greg P. Coffey, David A. Baker, Laura E. O'Dell, Janet Neisewander

Research output: Contribution to journalArticle

210 Scopus citations

Abstract

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 IV). 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 IP) 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.

Original languageEnglish (US)
Pages (from-to)48-59
Number of pages12
JournalNeuropsychopharmacology
Volume19
Issue number1
DOIs
StatePublished - Jul 1998

Keywords

  • Amygdala
  • Cocaine withdrawal
  • Cocaine-seeking behavior
  • Craving
  • Dopamine
  • Extinction
  • Reinstatement
  • Self-administration

ASJC Scopus subject areas

  • Pharmacology
  • Psychiatry and Mental health

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