Norepinephrine system at the interface of attention and reward.

Reward learning is key to survival for individuals. Attention plays an important role in the rapid recognition of reward cues and establishment of reward memories. Reward history reciprocally guides attention to reward stimuli. However, the neurological processes of the interplay between reward and attention remain largely elusive, due to the diversity of the neural substrates that participate in these two processes. In this review, we delineate the complex and differentiated locus coeruleus norepinephrine (LC-NE) system in relation to different behavioral and cognitive substrates of reward and attention. The LC receives reward related sensory, perceptual, and visceral inputs, releases NE, glutamate, dopamine and various neuropeptides, forms reward memories, drives attentional bias and selects behavioral strategies for reward. Preclinical and clinical studies have found that abnormalities in the LC-NE system are involved in a variety of psychiatric conditions marked by disturbed functions in reward and attention. Therefore, we propose that the LC-NE system is an important hub in the interplay between reward and attention as well as a critical therapeutic target for psychiatric disorders characterized by compromised functions in reward and attention.

Plastic change of prefrontal cortex mediates anxiety-like behaviors associated with chronic pain in neuropathic rats.

Clinical studies show that anxiety and chronic pain are concomitant. The neural basis for the comorbidity is unclear. The prefrontal cortex (PFC) has been recognized as a critical area for affective disorders and chronic pain modulation. In this study, we examined the role of the PFC in the pathogenesis of anxiety associated with chronic pain in a rat model of neuropathic pain with spare nerve injury (SNI). The SNI rats showed apparent anxiety-like behaviors in both open field (OF) test and elevated-plus maze (EPM) test eight weeks after surgery. Thus, the number of entries to the central area in the OF decreased to 45% (±5%, n = 15) of sham control (n = 17), while the overall motor activity (i.e., total distance) was unaffected. In the EPM, the percentage of entries into the open arms significantly (p < 0.001) decreased in SNI rats (SNI: 12.58 ± 2.7%, n = 15; sham: 30.75 ± 2.82%, n = 17), so did the time spent in the open arms (SNI: 4.35 ± 1.45%, n = 15; Sham: 11.65 ± 2.18%, n = 17). To explore the neural basis for the association between anxiety and chronic pain, local field potentials (LFPs) were recorded from the medial PFC (mPFC) and ventral hippocampus. In SNI rats, there were significantly greater increases in both theta-frequency power in the mPFC and theta-frequency synchronization between the mPFC and ventral hippocampus, when animals were displaying elevated anxiety-like behaviors in avoiding anxiogenic regions in EPM and OF chamber. Western blot analyses showed a significant elevation of serotonin transporter expression in the anxious SNI rats. Inhibition of serotonin transporter effectively alleviated anxiety-like behaviors following sub-chronic (15 days) treatment with systemic citalopram (10 mg/kg/day, intraperitoneally). Moreover, the anxiety-like behaviors in the SNI rats were also suppressed by direct mPFC application of serotonin. Taken together, we conclude that the plasticity of serotonin transmission in the mPFC likely contribute to the promotion of anxiety state associated with neuropathic pain.