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

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. Markovic et al. demonstrate in rodents that anhedonia-like states in inflammatory pain are mediated through increased inhibitory control and subsequent diminished activity of mesolimbic dopamine neurons.

Automated summary

Anhedonia-like states in inflammatory pain are mediated through decreased activity of mesolimbic dopamine neurons, which are triggered by increased inhibitory control from the rostromedial tegmental nucleus onto ventral tegmental area dopamine neurons. Selective activation of ventral tegmental area dopamine neurons can restore motivation and hedonic responses.