Medial Prefrontal Cortical Dopamine Responses During Operant Self-Administration of Sweetened Ethanol

Alcohol Clin Exp Res. 2016 Aug;40(8):1662-70. doi: 10.1111/acer.13141. Epub 2016 Jul 20.

Abstract

Background: Medial prefrontal cortex (mPFC) dysfunction is present in heavy alcohol consumers. Dopamine signaling in mPFC is associated with executive functioning and affects drinking behavior; however, direct measurement of extracellular mPFC dopamine during appetitive and consummatory ethanol (EtOH) self-administration behavior has not been reported.

Methods: We used in vivo microdialysis in freely behaving, adult, male, Long Evans rats to determine extracellular dopamine concentration in the mPFC during operant self-administration of an EtOH-plus-sucrose or sucrose solution. The model separated appetitive/seeking from consummatory phases of the operant session. Dopamine was also monitored in an untrained handling control group, and dialysate EtOH was measured in the EtOH-drinking group.

Results: Home cage baseline dopamine was lower in rats that experienced a week of drinking sweetened EtOH compared with sucrose-drinking and handling controls. Transfer into the operant chamber and the initiation of consumption stimulated a relatively higher change in dopamine over baseline in the sweetened EtOH group compared with sucrose and handling controls. However, all groups show a dopamine response during transfer into the operant chamber, and the sucrose group had a relatively higher change in dopamine over baseline during initiation of consumption compared with handling controls. The time courses of dopamine and EtOH in the mPFC differ in the EtOH-consuming rats.

Conclusions: Differences in extracellular mPFC dopamine between EtOH drinkers compared with control groups suggest that mPFC dopamine is involved in the mechanism of operant self-administration of sweetened EtOH and sucrose. Furthermore, the increase in dopamine during consumption is consistent with a role of mPFC dopamine in reward prediction.

Keywords: Appetitive; Consumption; Ethanol; Ethanol-Seeking; Mesocortical; Operant Self-Administration.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Conditioning, Operant / drug effects
  • Conditioning, Operant / physiology*
  • Dopamine / metabolism*
  • Ethanol / administration & dosage*
  • Male
  • Prefrontal Cortex / drug effects
  • Prefrontal Cortex / metabolism*
  • Rats
  • Rats, Long-Evans
  • Self Administration
  • Sweetening Agents / administration & dosage*

Substances

  • Sweetening Agents
  • Ethanol
  • Dopamine