Dramatically decreased cocaine self-administration in dopamine but not serotonin transporter knock-out mice

Morgane Thomsen, F. Scott Hall, George R. Uhl, S. Barak Caine

Research output: Contribution to journalArticle

Abstract

There has been much interest in the relative importance of dopamine and serotonin transporters in the abuse-related-effects of cocaine. We tested the hypotheses that mice lacking the dopamine transporter (DAT-/-), the serotonin transporter (SERT-/-), or both (DAT-/-SERT -/-) exhibit decreased reinforcing effects of cocaine. We also assessed whether observed effects on self-administration are specific to cocaine or if operant behavior maintained by food or a direct dopamine agonist are similarly affected. We used a broad range of experimental conditions that included acquisition without previous training, behavior established with food training and subsequent testing with food, cocaine or a direct dopamine agonist as reinforcers, fixed ratio and progressive ratio schedules of reinforcement, and a reversal procedure. Wild-type mice readily acquired cocaine self-administration and showed dose-response curves characteristic of the schedule of reinforcement that was used. While some DAT-/- mice appeared to acquire cocaine self-administration transiently, almost all DAT -/- mice failed to self-administer cocaine reliably. Food-maintained behaviors were not decreased by the DAT mutation, and IV self-administration of a direct dopamine agonist was robust in the DAT-/- mice. In contrast to those mice, cocaine's reinforcing effects were not diminished in SERT -/- mice under any of the conditions tested, except for impaired initial acquisition of both food- and cocaine-maintained behavior. These findings support the notion that the DAT, but not the SERT, is critical in mediating the reinforcing effects of cocaine.

Original languageEnglish (US)
Pages (from-to)1087-1092
Number of pages6
JournalJournal of Neuroscience
Volume29
Issue number4
DOIs
Publication statusPublished - Jan 28 2009
Externally publishedYes

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Keywords

  • Cocaine
  • DAT
  • Drug abuse
  • Knock-out mouse
  • Progressive ratio
  • SERT

ASJC Scopus subject areas

  • Neuroscience(all)

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