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 Citations (Scopus)

Abstract

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
Volume20
Issue number3
DOIs
StatePublished - May 1 2015

Fingerprint

Limbic System
Ventral Tegmental Area
Prosencephalon
Synaptic Transmission
Dopamine
Ethanol
Prefrontal Cortex
Nucleus Accumbens
Microinjections
Sulpiride
Dopamine Antagonists
Neurobiology
Dopaminergic Neurons
Dopamine Receptors
Basal Forebrain
Reward
Alcoholism
Alcohols

All Science Journal Classification (ASJC) codes

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

Cite this

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title = "The reinforcing effects of ethanol within the posterior ventral tegmental area depend on dopamine neurotransmission to forebrain cortico-limbic systems",
abstract = "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.'",
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The reinforcing effects of ethanol within the posterior ventral tegmental area depend on dopamine neurotransmission to forebrain cortico-limbic systems. / Ding, Zheng Ming; Ingraham, Cynthia M.; Rodd, Zachary A.; McBride, William J.

In: Addiction Biology, Vol. 20, No. 3, 01.05.2015, p. 458-468.

Research output: Contribution to journalArticle

TY - JOUR

T1 - The reinforcing effects of ethanol within the posterior ventral tegmental area depend on dopamine neurotransmission to forebrain cortico-limbic systems

AU - Ding, Zheng Ming

AU - Ingraham, Cynthia M.

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N2 - 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.'

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