mTORC1 in the orbitofrontal cortex promotes habitual alcohol seeking

Elife. 2019 Dec 11:8:e51333. doi: 10.7554/eLife.51333.

Abstract

The mechanistic target of rapamycin complex 1 (mTORC1) plays an important role in dendritic translation and in learning and memory. We previously showed that heavy alcohol use activates mTORC1 in the orbitofrontal cortex (OFC) of rodents (Laguesse et al., 2017a). Here, we set out to determine the consequences of alcohol-dependent mTORC1 activation in the OFC. We found that inhibition of mTORC1 activity in the OFC attenuates alcohol seeking and restores sensitivity to outcome devaluation in rats that habitually seek alcohol. In contrast, habitual responding for sucrose was unaltered by mTORC1 inhibition, suggesting that mTORC1's role in habitual behavior is specific to alcohol. We further show that inhibition of GluN2B in the OFC attenuates alcohol-dependent mTORC1 activation, alcohol seeking and habitual responding for alcohol. Together, these data suggest that the GluN2B/mTORC1 axis in the OFC drives alcohol seeking and habit.

Keywords: OFC; addiction; alcohol; mTOR; neuroscience; rat.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Alcoholism / physiopathology*
  • Animals
  • Behavior, Animal
  • Conditioning, Operant
  • Ethanol / metabolism
  • Mechanistic Target of Rapamycin Complex 1 / metabolism*
  • Prefrontal Cortex / enzymology*
  • Prefrontal Cortex / physiology*
  • Rats
  • Receptors, N-Methyl-D-Aspartate / metabolism

Substances

  • NR2B NMDA receptor
  • Receptors, N-Methyl-D-Aspartate
  • Ethanol
  • Mechanistic Target of Rapamycin Complex 1