Effects of Monoamine Uptake Inhibitors in an Assay of Pain Depressed Behavior in Male Mice

Abstract

Consequences of pain include stimulation of some behaviors (e.g. reflexive withdrawal from stimuli), and depression of others (e.g. exercise, and work). Pain depressed behaviors are among the primary diagnostic and treatment concerns for physicians, but preclinical research has often explored pain stimulated behaviors. This discrepancy between basic research and clinical application may be one obstacle to the development of new pain treatments. In the present study, we modeled pain-related depression of behavior by observing nesting behavior in male ICR mice. Nest building is an innate mouse behavior that is reduced when the mouse is exposed to a pain stimulus. Pain-related depression of nesting is blocked by the clinically effective nonsteroidal anti-inflammatory drug (NSAID) ketoprofen. This project examines effects of monoamine uptake inhibitors with varying selectivity for serotonin (5HT), norepinephrine (NE) and dopamine (DA) on pain-related depression of nesting. Citalopram (5HT-selective), nisoxetine (NE-selective), milnacipran (mixed action, 5HT/NE-selective), and bupropion (DA-selective) were evaluated for their ability to block pain-related depression of nesting. Results show that the monoamine uptake inhibitors lacking significant dopamine had no effect on pain-depressed nesting. This finding is consistent with previous work suggesting that dopamine may be a key neurochemical target in the treatment of pain-related depression of behavior. Funding Source: Department of Psychological Sciences