Pain induces adaptations in ventral tegmental area dopamine neurons to drive anhedonia-like behavior

Nat Neurosci. 2021 Nov;24(11):1601-1613. doi: 10.1038/s41593-021-00924-3. Epub 2021 Oct 18.


The persistence of negative affect in pain leads to co-morbid symptoms such as anhedonia and depression-major health issues in the United States. The neuronal circuitry and contribution of specific cellular populations underlying these behavioral adaptations remains unknown. A common characteristic of negative affect is a decrease in motivation to initiate and complete goal-directed behavior, known as anhedonia. We report that in rodents, inflammatory pain decreased the activity of ventral tegmental area (VTA) dopamine (DA) neurons, which are critical mediators of motivational states. Pain increased rostromedial tegmental nucleus inhibitory tone onto VTA DA neurons, making them less excitable. Furthermore, the decreased activity of DA neurons was associated with reduced motivation for natural rewards, consistent with anhedonia-like behavior. Selective activation of VTA DA neurons was sufficient to restore baseline motivation and hedonic responses to natural rewards. These findings reveal pain-induced adaptations within VTA DA neurons that underlie anhedonia-like behavior.

Publication types

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

MeSH terms

  • Adaptation, Physiological / physiology*
  • Anhedonia / physiology*
  • Animals
  • Conditioning, Operant / physiology
  • Dopaminergic Neurons / chemistry
  • Dopaminergic Neurons / metabolism*
  • Female
  • Male
  • Optogenetics / methods
  • Pain / genetics
  • Pain / metabolism*
  • Rats
  • Rats, Long-Evans
  • Rats, Transgenic
  • Ventral Tegmental Area / chemistry
  • Ventral Tegmental Area / metabolism*