Midbrain circuit regulation of individual alcohol drinking behaviors in mice

Nat Commun. 2017 Dec 20;8(1):2220. doi: 10.1038/s41467-017-02365-8.

Abstract

Alcohol-use disorder (AUD) is the most prevalent substance-use disorder worldwide. There is substantial individual variability in alcohol drinking behaviors in the population, the neural circuit mechanisms of which remain elusive. Utilizing in vivo electrophysiological techniques, we find that low alcohol drinking (LAD) mice have dramatically higher ventral tegmental area (VTA) dopamine neuron firing and burst activity. Unexpectedly, VTA dopamine neuron activity in high alcohol drinking (HAD) mice does not differ from alcohol naive mice. Optogenetically enhancing VTA dopamine neuron burst activity in HAD mice decreases alcohol drinking behaviors. Circuit-specific recordings reveal that spontaneous activity of nucleus accumbens-projecting VTA (VTA-NAc) neurons is selectively higher in LAD mice. Specifically activating this projection is sufficient to reduce alcohol consumption in HAD mice. Furthermore, we uncover ionic and cellular mechanisms that suggest unique neuroadaptations between the alcohol drinking groups. Together, these data identify a neural circuit responsible for individual alcohol drinking behaviors.

Publication types

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

MeSH terms

  • Alcohol Drinking / metabolism
  • Alcohol Drinking / physiopathology*
  • Animals
  • Behavior, Animal / physiology*
  • Dopaminergic Neurons / metabolism*
  • Mesencephalon / metabolism
  • Mesencephalon / physiopathology
  • Mice
  • Neural Pathways / physiology
  • Nucleus Accumbens / metabolism
  • Nucleus Accumbens / physiopathology*
  • Optogenetics
  • Ventral Tegmental Area / metabolism
  • Ventral Tegmental Area / physiopathology*