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Instrumental learning in a mouse model for obsessive-compulsive disorder: Impaired habit formation in Sapap3 mutants.
Neurobiology of Learning and Memory ( IF 2.2 ) Pub Date : 2020-01-09 , DOI: 10.1016/j.nlm.2020.107162
I Ehmer 1 , M Feenstra 1 , I Willuhn 1 , D Denys 1
Affiliation  

It has been hypothesized that maladaptive habit formation contributes to compulsivity in psychiatric disorders such as obsessive-compulsive disorder (OCD). Here, we used an established animal model of OCD, Sapap3 knockout mice (SAPAP3-/-), to investigate the balance of goal-directed and habitual behavior in compulsive individuals and if altered habit formation is associated with compulsive-like behavior. We subjected 24 SAPAP3-/- and 24 wildtype littermates (WT) to two different schedules of reinforcement in a within-subjects design: a random-ratio (RR) schedule to promote goal-directedness, and a random-interval (RI) schedule, known to facilitate habitual responding. SAPAP3-/- acquired responding under both schedules, but showed lower response rates and fewer attempts to collect food pellets than WT, indicative of altered reward processing. As expected, WT were sensitive to sensory-specific satiety (outcome devaluation) following RR training, but not RI training, demonstrating schedule-specific acquisition of goal-directed and habitual responding, respectively. In contrast, SAPAP3-/- were sensitive to outcome devaluation after both RR and RI training, suggesting decreased engagement of a habitual response strategy. No linear relation was observed between increased grooming and behavior during the outcome devaluation test in SAPAP3-/-. Together, our findings demonstrate altered reward processing and impaired habit learning in SAPAP3-/-. We report a diminished propensity to form habits in these mice, which albeit inconsistent with the predominant idea of excessive habit formation in OCD, nonetheless points at dysregulation of behavioral automation in the context of compulsivity. Thus, the habit hypothesis of compulsivity should be updated to state that an imbalance of habitual and goal-directed responding in either direction can contribute to the development of compulsive behavior.

中文翻译:

强迫症小鼠模型的工具学习:Sapap3突变体中不良习惯的形成。

据推测,不良适应习惯的形成有助于强迫症等强迫症的强迫症。在这里,我们使用已建立的强迫症动物模型Sapap3敲除小鼠(SAPAP3-/-),研究强迫性个体中目标导向和习惯性行为的平衡,以及是否改变了习惯形成与强迫性行为相关。在对象内部设计中,我们对24个SAPAP3-/-和24个野生型同窝仔(WT)进行了两种不同的加固计划:随机比率(RR)计划以促进目标导向,而随机间隔(RI)计划,以促进习惯性响应。SAPAP3-/-在两种计划下都获得了响应,但与WT相比,响应率更低,收集食物颗粒的尝试更少,这表明奖励处理发生了变化。正如预期的那样,WT对RR训练后对特定于感觉的饱腹感(结果贬值)敏感,但对RI训练不敏感,分别说明了针对目标的定向训练和习惯性反应的特定于日程表的获取。相反,在RR和RI训练后,SAPAP3-/-对结果贬值很敏感,表明习惯性反应策略的参与度降低。在SAPAP3-/-的结果贬值测试期间,没有发现增加的修饰与行为之间存在线性关系。总之,我们的发现表明SAPAP3-/-中奖励处理的改变和习惯学习的受损。我们报道了这些小鼠形成习惯的倾向降低了,尽管这与强迫症中过度习惯养成的主要观点不一致,但这种观点指向行为自动化的失调。从而,
更新日期:2020-01-09
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