Serotonin and Dopamine Show Different Response Profiles to Acute Stress in the Nucleus Accumbens and Medial Prefrontal Cortex of Rats with Neuropathic Pain.

The ability to adaptively guide behaviour requires the integration of external information with internal motivational factors. Decision-making capabilities can be impaired by acute stress and is often exacerbated by chronic pain. Chronic neuropathic pain patients often present with cognitive dysfunction, including impaired decision-making. The mechanisms underlying these changes are not well understood but may include altered monoaminergic transmission in the brain. In this study we investigated the relationships between dopamine, serotonin, and their metabolites in key brain regions that regulate motivated behaviour and decision-making. The neurochemical profiles of the medial prefrontal cortex, orbital prefrontal cortex, and nucleus accumbens were analysed using HPLC in rats that received a chronic constriction injury (CCI) of the right sciatic nerve and an acute stress (15-min restraint), prior to an outcome devaluation task. CCI alone significantly decreased dopamine but not serotonin concentrations in the medial prefrontal cortex. By contrast, restraint stress acutely increased dopamine in the medial prefrontal cortex, and the nucleus accumbens; and increased serotonin in the medial prefrontal cortex 2 h later. The sustained dopaminergic and serotonergic responses to acute stress highlight the importance of an animal's ability to mount an effective coping response. In addition, these data suggest that the impact of nerve injury and acute stress on outcome-devaluation occurs independently of dopaminergic and serotonergic transmission in the medial prefrontal cortex, orbital prefrontal cortex and nucleus accumbens of rats.