The reinforcing effects of ethanol within the posterior ventral tegmental area depend on dopamine neurotransmission to forebrain cortico-limbic systems

Zheng Ming Ding, Cynthia M. Ingraham, Zachary A. Rodd, William J. McBride

Research output: Contribution to journalArticle

17 Scopus citations


Ethanol can be self-infused directly into the posterior ventral tegmental area (pVTA) and these effects involve activation of local dopamine neurons. However, the neuro-circuitry beyond the pVTA involved in these reinforcing effects has not been explored. Intra-pVTA microinjection of ethanol increases dopamine release in the nucleus accumbens (NAC), medial prefrontal cortex (mPFC) and ventral pallidum (VP). The present study tested the hypothesis that the reinforcing effects of ethanol within the pVTA involve the activation of dopamine projections from the pVTA to the NAC, VP and mPFC. Following the acquisition of self-infusions of 200 mg% ethanol into the pVTA, either the dopamine D2 receptor antagonist sulpiride (0, 10 or 100 μM) or the D1 receptor antagonist SCH-23390 (0, 10 or 100 μM) was microinjected into the ipsilateral NAC shell (NACsh), NAC core (NACcr), VP or mPFC immediately prior to the self-infusion sessions to assess the involvement of the different dopamine projections in the reinforcing effects of ethanol. Microinjection of each compound at higher concentration into the NACsh, VP or mPFC, but not the NACcr, significantly reduced the responses on the active lever (from 40-50 to approximately 20 responses). These results indicate that activation of dopamine receptors in the NACsh, VP or mPFC, but not the NACcr, is involved in mediating the reinforcing effects of ethanol in the pVTA, suggesting that the 'alcohol reward' neuro-circuitry consist of, at least in part, activation of the dopamine projections from the pVTA to the NACsh, VP and mPFC. 'Identifying mechanisms involved in ethanol reinforcement is critical to understanding the neurobiology of alcohol abuse. Ethanol produces local reinforcing effects within the posterior ventral tegmental area (VTA). Here we investigated the neural circuits involved in these effects with microinjection of dopamine receptor antagonists into the corticolimbic regions receiving dopamine projections from the VTA, including nucleus accumbens shell, ventral pallidum and medial prefrontal cortex. Such treatments attenuated self-infusion of ethanol into the VTA, indicating an important role of feed-forward dopamine systems in reinforcing effects of ethanol.'

Original languageEnglish (US)
Pages (from-to)458-468
Number of pages11
JournalAddiction Biology
Issue number3
StatePublished - May 1 2015



  • Dopamine D1 receptor
  • dopamine D2 receptor
  • ethanol
  • intra-cranial self-administration
  • medial prefrontal cortex
  • nucleus accumbens
  • ventral pallidum
  • ventral tegmental area.

ASJC Scopus subject areas

  • Medicine (miscellaneous)
  • Pharmacology
  • Psychiatry and Mental health

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