Preclinical Laboratory, Department of Adult Psychiatry and Psychotherapy, University Hospital of Psychiatry and University of Zurich, Zurich, Switzerland.
Zurich Neuroscience Center, University of Zurich and ETH Zurich, Zurich, Switzerland.
Commun Biol. 2024 Aug 9;7(1):966. doi: 10.1038/s42003-024-06658-9.
Whilst reward pathologies are major and common in stress-related neuropsychiatric disorders, their neurobiology and treatment are poorly understood. Imaging studies in human reward pathology indicate attenuated BOLD activity in nucleus accumbens (NAc) coincident with reward anticipation but not reinforcement; potentially, this is dopamine (DA) related. In mice, chronic social stress (CSS) leads to reduced reward learning and motivation. Here, DA-sensor fibre photometry is used to investigate whether these behavioural deficits co-occur with altered NAc DA activity during reward anticipation and/or reinforcement. In CSS mice relative to controls: (1) Reduced discriminative learning of the sequence, tone-on + appetitive behaviour = tone-on + sucrose reinforcement, co-occurs with attenuated NAc DA activity throughout tone-on and sucrose reinforcement. (2) Reduced motivation during the sequence, operant behaviour = tone-on + sucrose delivery + sucrose reinforcement, co-occurs with attenuated NAc DA activity at tone-on and typical activity at sucrose reinforcement. (3) Reduced motivation during the sequence, operant behaviour = appetitive behaviour + sociosexual reinforcement, co-occurs with typical NAc DA activity at female reinforcement. Therefore, in CSS mice, low NAc DA activity co-occurs with low reward anticipation and could account for deficits in learning and motivation, with important implications for understanding human reward pathology.
虽然奖励病理学在与应激相关的神经精神疾病中是主要和常见的,但它们的神经生物学和治疗方法还了解甚少。人类奖励病理学的影像学研究表明,与奖励预期但不强化相关的伏隔核(NAc)中 BOLD 活性减弱;潜在地,这与多巴胺(DA)有关。在小鼠中,慢性社会应激(CSS)导致奖励学习和动机减少。在这里,使用 DA 传感器光纤光度法来研究这些行为缺陷是否与奖励预期和/或强化期间 NAc DA 活性的改变同时发生。与对照组相比,CSS 小鼠:(1)对序列的辨别学习减少,即音调开启+食欲行为=音调开启+蔗糖强化,同时伴随着 NAc DA 活性在整个音调开启和蔗糖强化过程中减弱。(2)在序列中,操作性行为=音调开启+蔗糖传递+蔗糖强化期间的动机降低,与音调开启和典型蔗糖强化时 NAc DA 活性减弱同时发生。(3)在序列中,操作性行为=食欲行为+社交性强化期间的动机降低,与女性强化时 NAc DA 活性典型同时发生。因此,在 CSS 小鼠中,低 NAc DA 活性与低奖励预期同时发生,可能导致学习和动机缺陷,这对理解人类奖励病理学具有重要意义。