{"title":"The role of fear and dopamine-striatal pathways in grooming","authors":"Lior Givon , Shahaf Edut , Oded Klavir","doi":"10.1016/j.neuropharm.2025.110323","DOIUrl":null,"url":null,"abstract":"<div><div>Fear is a fundamental emotion that triggers rapid and automatic behavioral response. Fear is known to suppress reward-seeking behaviors, interrupt previous activities to prioritize defensive responses and lead to rapid switch to defensive reactions. Dopamine (DA) plays a complicated role in the choice and performance of actions and it has a potential interaction of innate actions with the presence of fear. Here, in a series of experiments we explore the role of the different DA striatal pathways in mediating grooming, an innate behavior comprised of a structured sequence of repetitive actions, with or without the presence of fear. Using chemogenetics, we specifically inhibited the DA pathways projecting to the dorsolateral striatum (DLS), dorsomedial striatum (DMS), and ventral striatum (VS), while mice were engaged in a behavioral paradigm inducing grooming during the presentation of a fear related cue. We found that fear related cues consistently reduced grooming proportions and shortened induced grooming bouts, regardless of DA manipulation, indicating prioritization of freezing behavior in fearful contexts. This also suggests that fear responses may be mediated through pathways independent of DA-based action selection. The role of DA, however, varies depending on the specific striatal pathway. Inhibiting DLS DA input delayed grooming initiation and reduced grooming when competing with freezing. In contrast, DMS DA input had no effect on grooming, while inhibition of VS mesolimbic DA input increased grooming proportions and duration. These findings underscore the distinct and sometimes opposing roles of different DA-striatal pathways in modulating innate behaviors. We discuss potential implications of this duality in DA function for both theoretical and clinical fields.</div></div>","PeriodicalId":19139,"journal":{"name":"Neuropharmacology","volume":"269 ","pages":"Article 110323"},"PeriodicalIF":4.6000,"publicationDate":"2025-01-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Neuropharmacology","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S0028390825000292","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"NEUROSCIENCES","Score":null,"Total":0}
引用次数: 0
Abstract
Fear is a fundamental emotion that triggers rapid and automatic behavioral response. Fear is known to suppress reward-seeking behaviors, interrupt previous activities to prioritize defensive responses and lead to rapid switch to defensive reactions. Dopamine (DA) plays a complicated role in the choice and performance of actions and it has a potential interaction of innate actions with the presence of fear. Here, in a series of experiments we explore the role of the different DA striatal pathways in mediating grooming, an innate behavior comprised of a structured sequence of repetitive actions, with or without the presence of fear. Using chemogenetics, we specifically inhibited the DA pathways projecting to the dorsolateral striatum (DLS), dorsomedial striatum (DMS), and ventral striatum (VS), while mice were engaged in a behavioral paradigm inducing grooming during the presentation of a fear related cue. We found that fear related cues consistently reduced grooming proportions and shortened induced grooming bouts, regardless of DA manipulation, indicating prioritization of freezing behavior in fearful contexts. This also suggests that fear responses may be mediated through pathways independent of DA-based action selection. The role of DA, however, varies depending on the specific striatal pathway. Inhibiting DLS DA input delayed grooming initiation and reduced grooming when competing with freezing. In contrast, DMS DA input had no effect on grooming, while inhibition of VS mesolimbic DA input increased grooming proportions and duration. These findings underscore the distinct and sometimes opposing roles of different DA-striatal pathways in modulating innate behaviors. We discuss potential implications of this duality in DA function for both theoretical and clinical fields.
期刊介绍:
Neuropharmacology publishes high quality, original research and review articles within the discipline of neuroscience, especially articles with a neuropharmacological component. However, papers within any area of neuroscience will be considered. The journal does not usually accept clinical research, although preclinical neuropharmacological studies in humans may be considered. The journal only considers submissions in which the chemical structures and compositions of experimental agents are readily available in the literature or disclosed by the authors in the submitted manuscript. Only in exceptional circumstances will natural products be considered, and then only if the preparation is well defined by scientific means. Neuropharmacology publishes articles of any length (original research and reviews).