, Volume 186, Issue 1, pp 82–92 | Cite as

Effects of dexfenfluramine and 5-HT3 receptor antagonists on stress-induced reinstatement of alcohol seeking in rats

  • Anh Dzung Lê
  • Douglas Funk
  • Stephen Harding
  • W. Juzytsch
  • Paul J. Fletcher
  • Yavin Shaham
Original Investigation


Rationale and objectives

We previously found that systemic injections of the 5-HT uptake blocker fluoxetine attenuate intermittent footshock stress-induced reinstatement of alcohol seeking in rats, while inhibition of 5-HT neurons in the median raphe induces reinstatement of alcohol seeking. In this study, we further explored the role of 5-HT in footshock stress-induced reinstatement of alcohol seeking by determining the effects of the 5-HT releaser and reuptake blocker dexfenfluramine, and the 5-HT receptor antagonists ondansetron and tropisetron, which decrease alcohol self-administration and anxiety-like responses in rats, on this reinstatement.


Different groups of male Wistar rats were trained to self-administer alcohol (12% v/v) for 28–31 days (1 h/day, 0.19 ml per alcohol delivery) and then their lever responding for alcohol was extinguished over 9–10 days. Subsequently, the effect of systemic injections of vehicle or dexfenfluramine (0.25 or 0.5 mg/kg, i.p), ondansetron (0.001, 0.01, or 0.1 mg/kg, i.p), or tropisetron (0.001, 0.01, and 0.1 mg/kg, i.p) on reinstatement induced by 10 min of intermittent footshock (0.8 mA) was determined.


Systemic injections of dexfenfluramine, ondansetron or tropisetron attenuated footshock-induced reinstatement of alcohol seeking. Injections of dexfenfluramine, ondansetron, or tropisetron had no effect on extinguished lever responding in the absence of footshock.


The present results provide additional support for the hypothesis that brain 5-HT systems are involved in stress-induced reinstatement of alcohol seeking. The neuronal mechanisms that potentially mediate the unexpected observation that both stimulation of 5-HT release and blockade of 5-HT3 receptors attenuate footshock-induced reinstatement are discussed.


5-Hydroxytryptamine Reinstatement Footshock 5-HT3 receptors Relapse Stress 



This work was supported by a grant from the NIAAA (AA13108) to A.D. Le.


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Copyright information

© Springer-Verlag 2006

Authors and Affiliations

  • Anh Dzung Lê
    • 1
    • 2
    • 3
  • Douglas Funk
    • 1
  • Stephen Harding
    • 1
  • W. Juzytsch
    • 1
  • Paul J. Fletcher
    • 1
    • 3
    • 4
  • Yavin Shaham
    • 5
  1. 1.Department of NeuroscienceCentre for Addiction and Mental HealthTorontoCanada
  2. 2.Department of PharmacologyUniversity of TorontoTorontoCanada
  3. 3.Department of PsychiatryUniversity of TorontoTorontoCanada
  4. 4.Department of PsychologyUniversity of TorontoTorontoCanada
  5. 5.Behavioral Neuroscience BranchIRP/NIDA/NIH/DHHSBaltimoreUSA

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