Preference for a cocaine-associated environment is attenuated by augmented accumbal serotonin in cocaine withdrawn rats

G. C. Harris, K. Altomare, G. Aston-Jones

Research output: Contribution to journalArticle

27 Scopus citations


Rationale: Recent studies have found decreased serotonin (5-HT) transmission within the nucleus accumbens following withdrawal from chronic cocaine. Objective: We sought to investigate whether increasing brain 5-HT levels would decrease behavioral responses that occur following cocaine withdrawal, namely increased preference for a cocaine environment and anxiety. Methods: The conditioned place preference and the defensive burying paradigms were used to measure the behavioral responses that occur 1 week following cocaine withdrawal. Results: We show that pharmacological agents that increase 5-HT transmission (sertraline or 5-hydoxytryptophan, 5-HTP) abolish the preference of subchronically cocaine-treated, abstinent rats for a cocaine-associated environment. Similar results were seen when sertraline was microinjected into the nucleus accumbens. Conversely, rats acutely conditioned with cocaine showed an increased preference for a cocaine-associated environment when pretreated with these drugs. Sertraline also decreased the heightened anxiety-like behaviors found in subchronically treated cocaine rats. Conclusions: These results indicate that drugs that augment 5-HT function may reduce the desire for cocaine following cocaine withdrawal, and thus facilitate cocaine abstinence in dependent subjects.

Original languageEnglish (US)
Pages (from-to)14-22
Number of pages9
Issue number1
Publication statusPublished - Jan 1 2001
Externally publishedYes


All Science Journal Classification (ASJC) codes

  • Pharmacology


  • 5-HTP
  • Cocaine
  • Place conditioning
  • Serotonin
  • Sertraline
  • Withdrawal

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