Deficits in motivated behavior in a mouse model of paclitaxel-induced neuropathic pain

Paclitaxel is widely used in chemotherapy for common cancers. However, its administration is frequently associated with chronic pain and subsequent depression, anxiety, and lack of motivation, all of which lead to difficulties in the social lives of patients. In mouse models of paclitaxel-induced neuropathy, mechanical allodynia emerges within several days after intraperitoneal injections of paclitaxel, followed by depression- and anxiety-like behaviors. However, whether they show deficits in motivated behavior during this period and whether the time course of their symptoms is related to pain behavior remain unclear. Here, we investigated changes in locomotor-based behavioral performance. Before paclitaxel injection, the mice were trained to perform an operant conditioning task. In this task, they were water-restricted and head-fixed on a polystyrene disc, and spontaneous running was initiated to trigger a trial. After paclitaxel injection, changes in task performance were examined for 4 weeks. These mice exhibited mechanical hypersensitivity within the first week; however, a decline in the task success rate became evident after the second week. Subsequently, from the third week, the number of trials, the lick rate of anticipatory licking and the locomotor speed toward the reward decreased in the paclitaxel-treated mice compared with those in the vehicle-treated mice. Moreover, in paclitaxel-treated mice, resting-state c-Fos level during the behavioral impairment period was increased in the amygdala, which is implicated in emotion and motivated behaviors. These results demonstrate that in paclitaxel-treated mice, reduced reward expectation and impaired goal-directed behavior can be observed one week after the onset of pain-related behavior.