The reinforcing effects of ethanol within the prelimbic cortex and ethanol drinking: Involvement of local dopamine D2 receptor-mediated neurotransmission

Eric A. Engleman, Cynthia M. Ingraham, Zachary A. Rodd, James M. Murphy, William J. McBride, Zheng Ming Ding

Research output: Contribution to journalArticlepeer-review


Previous studies have identified important mesolimbic regions in supporting the reinforcing effects of ethanol. However, the involvement of the medial prefrontal cortex (mPFC), another key region within the mesocorticolimbic system, in ethanol reinforcement has been understudied. The objective of the current study was to examine the role of the prelimbic (PL) cortex sub-region of the mPFC in ethanol reinforcement and drinking. Intracranial self-administration was used to examine the reinforcing effects of ethanol within the PL cortex. Quantitative microdialysis was used to measure basal extracellular DA concentrations and clearance in the PL cortex following chronic ethanol drinking. In addition, the involvement of dopamine (DA) D2 receptors within the PL cortex on the reinforcing effects of ethanol and ethanol drinking was determined. Ethanol was dose-dependent self-administered into the PL cortex, with significantly more infusions elicited by 100−200 mg% ethanol than vehicle. Co-infusion of the D2 receptor antagonist sulpiride significantly reduced ethanol self-administration. Chronic ethanol drinking significantly elevated basal extracellular DA concentrations without altering DA clearance. Microinjection of sulpiride into the PL cortex selectively reduced ethanol, but not saccharine, drinking. These results indicate that the PL cortex supported the reinforcing effects of ethanol, and that ethanol drinking enhanced basal DA neurotransmission within the PL cortex. In addition, D2 receptor antagonism within the PL cortex reduced ethanol self-administration and drinking. Collectively, these findings revealed important DA mechanisms within the PL cortex in mediating ethanol reinforcement and drinking.

Original languageEnglish (US)
Article number108165
JournalDrug and alcohol dependence
StatePublished - Sep 1 2020

All Science Journal Classification (ASJC) codes

  • Toxicology
  • Pharmacology
  • Psychiatry and Mental health
  • Pharmacology (medical)

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