Pain induces adaptations in ventral tegmental area dopamine neurons to drive anhedonia-like behavior
- 18 October 2021
- journal article
- research article
- Published by Springer Science and Business Media LLC in Nature Neuroscience
- Vol. 24 (11), 1601-1613
- https://doi.org/10.1038/s41593-021-00924-3
Abstract
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.Keywords
This publication has 50 references indexed in Scilit:
- Pain relief produces negative reinforcement through activation of mesolimbic reward–valuation circuitryProceedings of the National Academy of Sciences of the United States of America, 2012
- Activation of VTA GABA Neurons Disrupts Reward ConsumptionNeuron, 2012
- Relief as a Reward: Hedonic and Neural Responses to Safety from PainPLOS ONE, 2011
- Dopamine in Motivational Control: Rewarding, Aversive, and AlertingNeuron, 2010
- The Rostromedial Tegmental Nucleus (RMTg), a GABAergic Afferent to Midbrain Dopamine Neurons, Encodes Aversive Stimuli and Inhibits Motor ResponsesNeuron, 2009
- A common neurobiology for pain and pleasureNature Reviews Neuroscience, 2008
- Decreased Central μ-Opioid Receptor Availability in FibromyalgiaJournal of Neuroscience, 2007
- Behavioral dopamine signalsTrends in Neurosciences, 2007
- Differential involvement of endogenous opioids in sucrose consumption and food reinforcementPharmacology Biochemistry and Behavior, 2006
- A Neural Substrate of Prediction and RewardScience, 1997