Selective serotonin reuptake inhibitors enhance cocaine-induced locomotor activity and dopamine release in the nucleus accumbens

M. J. Bubar, L. R. McMahon, P. De Deurwaerdère, U. Spampinato, K. A. Cunningham

Research output: Contribution to journalArticle

47 Scopus citations


The role for serotonin (5-HT) in mediating the behavioral effects of cocaine may be related in part to the ability of 5-HT to modulate the function of the dopamine (DA) mesoaccumbens pathways. In the present study, the ability of the selective serotonin reuptake inhibitors (SSRIs) fluoxetine (10 mg/kg, IP) and fluvoxamine (10 and 20 mg/kg, IP) to alter cocaine (10 mg/kg, IP)-induced hyperactivity and DA release in the nucleus accumbens (NAc) was analyzed in male Sprague-Dawley rats. Systemic administration of either fluoxetine or fluvoxamine enhanced cocaine-induced locomotor activity in a dose-dependent manner; fluoxetine (10 mg/kg, IP) also enhanced cocaine (10 mg/kg, IP)-induced DA efflux in the NAc. To test the hypothesis that the NAc serves as the locus of action underlying these effects following systemic cocaine administration, fluoxetine (1 and 3 μg/0.2 μl/side) or fluvoxamine (1 and 3 μg/0.2 μl/side) was microinfused into the NAc shell prior to systemic administration of cocaine (10 mg/kg, IP). Intra-NAc shell infusion of 3 μg of fluoxetine or fluvoxamine enhanced cocaine-induced hyperactivity, while infusion of fluoxetine (1 μM) through the microdialysis probe implanted into the NAc shell enhanced cocaine (10 mg/kg, IP)-induced DA efflux in the NAc. Thus, the ability of systemic injection of SSRIs to enhance cocaine-evoked hyperactivity and DA efflux in the NAc is mediated in part by local actions of the SSRIs in the NAc.

Original languageEnglish (US)
Pages (from-to)342-353
Number of pages12
Issue number3
StatePublished - Mar 2003



  • Cocaine
  • Dopamine microdialysis
  • Fluoxetine
  • Fluvoxamine
  • Locomotor activity
  • Nucleus accumbens

ASJC Scopus subject areas

  • Pharmacology
  • Cellular and Molecular Neuroscience

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