, Volume 204, Issue 3, pp 477–488

The role of noradrenaline and 5-hydroxytryptamine in yohimbine-induced increases in alcohol-seeking in rats


    • Neuroscience DepartmentCentre for Addiction and Mental Health
    • Department of PharmacologyUniversity of Toronto
    • Department of PsychiatryUniversity of Toronto
  • Douglas Funk
    • Neuroscience DepartmentCentre for Addiction and Mental Health
  • Stephen Harding
    • Neuroscience DepartmentCentre for Addiction and Mental Health
  • Walter Juzytsch
    • Neuroscience DepartmentCentre for Addiction and Mental Health
  • Paul J. Fletcher
    • Neuroscience DepartmentCentre for Addiction and Mental Health
    • Department of PsychiatryUniversity of Toronto
    • Department of PsychologyUniversity of Toronto
Original Investigation

DOI: 10.1007/s00213-009-1481-z

Cite this article as:
Dzung Lê, A., Funk, D., Harding, S. et al. Psychopharmacology (2009) 204: 477. doi:10.1007/s00213-009-1481-z


Rationale and objectives

We previously showed that systemic administration of the prototypical alpha-2 noradrenaline (NA) receptor antagonist yohimbine increases alcohol self-administration and reinstatement. Yohimbine also acts as an agonist of 5-hydroxytryptamine (5-HT) 5-HT1A receptors, which have been shown to be involved in alcohol seeking. Here, we determined the contributions of the alpha-2 and 5-HT1A properties of yohimbine to its effects on alcohol seeking.


The effects of lesions of the dorsal or ventral NA bundles with 6-OHDA on yohimbine-induced alcohol self-administration were first determined in male Wistar rats trained to self-administer alcohol (12% w/v, 0.19 ml per alcohol delivery), and then on reinstatement induced by yohimbine after extinction of the operant response. It was then determined whether the selective alpha-2 antagonist RS-79948 (0.1, 0.2, 0.4 mg/kg) would mimic the effects of yohimbine on self-administration and reinstatement. The effects of the alpha-2 receptor agonist clonidine, or the 5-HT1A antagonist WAY 100,635 were then determined on yohimbine-induced self-administration and reinstatement.


Lesions of the NA systems did not affect yohimbine-induced alcohol self-administration or reinstatement, and RS-79948 did not mimic the effects of yohimbine. Clonidine did not significantly affect increased alcohol self-administration induced by yohimbine, but did attenuate its effects on reinstatement. Blockade of 5-HT1A receptors reduced both yohimbine-induced self-administration and reinstatement.


These results suggest that alpha-2 antagonist properties of yohimbine may play a role in the reinstatement of alcohol-seeking, but not self-administration. On the other hand, yohimbine's actions on 5-HT1A receptors contribute to its effects on both alcohol self-administration and reinstatement.


AlcoholDrug abuseNorepinephrineRatRelapseSelf-administrationSerotoninSerotonin receptor

Copyright information

© Springer-Verlag 2009