Voluntary adolescent drinking enhances excitation by low levels of alcohol in a subset of dopaminergic neurons in the ventral tegmental area

Neuropharmacology. 2016 Nov;110(Pt A):386-395. doi: 10.1016/j.neuropharm.2016.07.031. Epub 2016 Jul 27.

Abstract

Enhanced dopamine (DA) neurotransmission from the ventral tegmental area (VTA) to the ventral striatum is thought to drive drug self-administration and mediate positive reinforcement. We examined neuronal firing rates in slices of mouse midbrain following adolescent binge-like alcohol drinking and find that prior alcohol experience greatly enhanced the sensitivity to excitation by ethanol itself (10-50 mM) in a subset of ventral midbrain DA neurons located in the medial VTA. This enhanced response after drinking was not associated with alterations of firing rate or other measures of intrinsic excitability. In addition, the phenomenon appears to be specific to adolescent drinking, as mice that established a drinking preference only after the onset of adulthood showed no change in alcohol sensitivity. Here we demonstrate not only that drinking during adolescence induces enhanced alcohol sensitivity, but also that this DA neuronal response occurs over a range of alcohol concentrations associated with social drinking in humans.

Keywords: Adolescence; Dopamine; Electrophysiology; Ethanol self-administration; Ventral tegmental area.

Publication types

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

MeSH terms

  • Action Potentials / drug effects
  • Alcohol Drinking / pathology
  • Alcohol Drinking / physiopathology
  • Animals
  • Binge Drinking / pathology
  • Binge Drinking / physiopathology*
  • Central Nervous System Depressants / toxicity*
  • Choice Behavior
  • Disease Models, Animal
  • Dopaminergic Neurons / drug effects*
  • Dopaminergic Neurons / pathology
  • Dopaminergic Neurons / physiology
  • Dose-Response Relationship, Drug
  • Ethanol / toxicity*
  • Green Fluorescent Proteins / genetics
  • Green Fluorescent Proteins / metabolism
  • Male
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Substance Withdrawal Syndrome / pathology
  • Substance Withdrawal Syndrome / physiopathology
  • Tyrosine 3-Monooxygenase / genetics
  • Tyrosine 3-Monooxygenase / metabolism
  • Ventral Tegmental Area / drug effects*
  • Ventral Tegmental Area / growth & development*
  • Ventral Tegmental Area / pathology
  • Ventral Tegmental Area / physiopathology
  • Volition

Substances

  • Central Nervous System Depressants
  • Green Fluorescent Proteins
  • Ethanol
  • Tyrosine 3-Monooxygenase