Increase in Nucleus Accumbens Dopamine Levels Following Local Ethanol Administration Is Not Mediated by Acetaldehyde

  1. Rhona B.C. Clarke1,*,
  2. Louise Adermark1,
  3. PeiPei Chau1,
  4. Bo Söderpalm1,2 and
  5. Mia Ericson1
  1. 1Addiction Biology Unit, Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
  2. 2Beroendekliniken, Sahlgrenska University Hospital, Gothenburg, Sweden
  1. *Corresponding author: Addiction Biology Unit, Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, PO Box 410, 405 30 Gothenburg, Sweden. Tel.: +46-31-786-39-19; Fax: +46-31-82-81-63; E-mail: rhona.clarke{at}
  • Received April 11, 2014.
  • Revision requested May 27, 2014.
  • Revision received June 11, 2014.
  • Accepted June 26, 2014.

Aims: Ethanol (EtOH) activates the mesolimbic dopamine system and increases dopamine levels in the nucleus accumbens (nAc), which is believed to underlie the rewarding effects of alcohol. Accumulating evidence now implicates that acetaldehyde, the first metabolite of EtOH, may play an important role in mediating some of the rewarding properties of its parent compound. The objective of this study was to investigate if the increase in accumbal dopamine output observed when administering EtOH locally in the nAc by reversed microdialysis is mediated by acetaldehyde. Methods: Acetaldehyde (1, 10, 100 or 200 µM) or EtOH (300 mM) was administered via reversed microdialysis in the nAc of male Wistar rats. In a separate experiment, animals were administered EtOH (300 mM) in the nAc, following pre-treatment with the acetaldehyde-sequestering agent d-penicillamine (50 mg/kg injected intraperitoneally 60 min before drug challenge). Microdialysates from the nAc were collected every 20 min and dopamine content was quantified using high-performance liquid chromatography. Results: Acetaldehyde administered in the nAc did not influence accumbal dopamine levels at any of the concentrations applied, whereas EtOH induced a significant increase in accumbal dopamine. The dopamine-elevating properties of EtOH were not attenuated by pre-treatment with d-penicillamine. Conclusion: The current results show that EtOH administered in the nAc induces an elevation in accumbal dopamine levels, which is not mimicked by acetaldehyde alone, nor is it influenced by acetaldehyde sequestering. This would suggest that the increase in accumbal dopamine following nAc EtOH administration is not mediated by acetaldehyde.