Chronic administration of methocinnamox, a mu-opioid receptor antagonist, reduces hedonic response without impacting motivation in mice.

Rationale: Genetic and pharmacological studies suggest that signaling through the mu opioid receptor (MOR) is essential for motivation to seek, and hedonic response to, both drugs of abuse as well as natural rewards. Given that impairments in hedonic reactivity and motivation are key behavioral features of depression, we wondered whether sustained deficits in endogenous opioid signaling in adulthood could produce these 'depression-related' behavioral phenotypes.

Objectives: To investigate the effect of chronic MOR blockade in adulthood on motivation and hedonic response to a food reward, as well as whether these behavioral variables are correlated at the individual animal level.

Methods: We chronically administered the pseudo-irreversible MOR antagonist methocinnamox (MCAM) for three weeks prior to assessing motivation and hedonic reactivity for a food reward in the progressive ratio and lickometer tasks, respectively. We then assessed whether motivation and hedonic response to reward were correlated at the individual animal level.

Results: Chronic administration of MCAM decreased hedonic response, while leaving goal-directed motivation intact. In addition, there was a weak negative correlation between motivation and hedonic response in individual mice treated with chronic MCAM, but not control mice.

Conclusions: Chronic blockade of the MOR decreases hedonic response, without impacting motivation to work for the same reward. Although the different components of reward processing such as motivation and hedonic response may be related, they appear to be dissociable.