Sheikh Misbah, Cambre Emily, Langreck Cory, Javitch Jonathan A, Canetta Sarah E
Department of Neuroscience, Barnard College, New York, NY, USA.
Division of Developmental Neuroscience, Department of Psychiatry, Columbia University Irving Medical Center and the New York State Psychiatric Institute, 1051 Riverside Drive, New York, NY, 10032, USA.
Psychopharmacology (Berl). 2025 May 10. doi: 10.1007/s00213-025-06801-2.
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.
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.
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.
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.
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.
基因和药理学研究表明，通过μ阿片受体（MOR）的信号传导对于寻求药物和滥用药物以及自然奖励的动机和享乐反应至关重要。鉴于享乐反应性和动机受损是抑郁症的关键行为特征，我们想知道成年期内源性阿片信号的持续缺陷是否会产生这些“与抑郁症相关”的行为表型。
研究成年期慢性MOR阻断对食物奖励的动机和享乐反应的影响，以及这些行为变量在个体动物水平上是否相关。
在分别通过累进比率和舔舐计任务评估对食物奖励的动机和享乐反应性之前，我们长期给予伪不可逆MOR拮抗剂甲氧辛胺（MCAM）三周。然后，我们评估了在个体动物水平上对奖励的动机和享乐反应是否相关。
长期给予MCAM会降低享乐反应，而目标导向的动机保持不变。此外，在长期接受MCAM治疗的个体小鼠中，动机与享乐反应之间存在微弱的负相关，但在对照小鼠中则不存在。
MOR的慢性阻断会降低享乐反应，而不会影响为获得相同奖励而工作的动机。虽然奖励处理的不同组成部分，如动机和享乐反应可能相关，但它们似乎是可分离的。
