Effects of monoamine uptake inhibitors on pain-related depression of nesting in mice

Pain is a significant public health problem, and assessment of pain-related impairment of behavior is a key clinical indicator and treatment target. Similar to opioids and NSAIDs, dopamine (DA) transporter inhibitors block pain-related depression of intracranial self-stimulation (ICSS) in rats. The primary goal of the present study was to determine if the effects of monoamine uptake inhibitors on pain-related depression of ICSS in rats extend to an assay of pain-related depression of nesting in mice. We hypothesized that the DA transporter-selective uptake inhibitor bupropion would block depression of nesting behavior produced by intraperitoneal injection of lactic acid, whereas selective serotonin transporter-selective citalopram, norepinephrine transporter-selective nisoxetine, and the mixed action selective serotonin transporter/norepinephrine transporter inhibitor milnacipran would be ineffective. Effects of the NSAID ketoprofen were also obtained to facilitate interpretation of the effects of the monoamine uptake inhibitors. Consistent with previous findings, ketoprofen blocked pain-related depression of nesting. In contrast, none of the monoamine uptake inhibitors blocked pain-related depression of nesting, although they all blocked pain-related stimulation of stretching. Unlike findings from studies of pain-related depression of ICSS, these results do not support consideration of DA uptake inhibitors for treatment of pain-related depression of behavior.