CHL1 depletion affects dopamine receptor D2-dependent modulation of mouse behavior
IntroductionThe dopaminergic system plays a key role in the appropriate functioning of the central nervous system, where it is essential for emotional balance, arousal, reward, and motor control. The cell adhesion molecule close homolog of L1 (CHL1) contributes to dopaminergic system development, an...
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| Format: | Article |
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Frontiers Media S.A.
2023-11-01
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| Series: | Frontiers in Behavioral Neuroscience |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fnbeh.2023.1288509/full |
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| author | Luciana Fernandes Ralf Kleene Ludovica Congiu Sandra Freitag Matthias Kneussel Gabriele Loers Melitta Schachner |
| author_facet | Luciana Fernandes Ralf Kleene Ludovica Congiu Sandra Freitag Matthias Kneussel Gabriele Loers Melitta Schachner |
| author_sort | Luciana Fernandes |
| collection | DOAJ |
| description | IntroductionThe dopaminergic system plays a key role in the appropriate functioning of the central nervous system, where it is essential for emotional balance, arousal, reward, and motor control. The cell adhesion molecule close homolog of L1 (CHL1) contributes to dopaminergic system development, and CHL1 and the dopamine receptor D2 (D2R) are associated with mental disorders like schizophrenia, addiction, autism spectrum disorder and depression.MethodsHere, we investigated how the interplay between CHL1 and D2R affects the behavior of young adult male and female wild-type (CHL+/+) and CHL1-deficient (CHL1−/−) mice, when D2R agonist quinpirole and antagonist sulpiride are applied.ResultsLow doses of quinpirole (0.02 mg/kg body weight) induced hypolocomotion of CHL1+/+ and CHL1−/− males and females, but led to a delayed response in CHL1−/− mice. Sulpiride (1 mg/kg body weight) affected locomotion of CHL1−/− females and social interaction of CHL1+/+ females as well as social interactions of CHL1−/− and CHL1+/+ males. Quinpirole increased novelty-seeking behavior of CHL1−/− males compared to CHL1+/+ males. Vehicle-treated CHL1−/− males and females showed enhanced working memory and reduced stress-related behavior.DiscussionWe propose that CHL1 regulates D2R-dependent functions in vivo. Deficiency of CHL1 leads to abnormal locomotor activity and emotionality, and to sex-dependent behavioral differences. |
| first_indexed | 2024-03-11T11:11:39Z |
| format | Article |
| id | doaj.art-7787825084824f3493f07bd5c1b8cd29 |
| institution | Directory Open Access Journal |
| issn | 1662-5153 |
| language | English |
| last_indexed | 2024-03-11T11:11:39Z |
| publishDate | 2023-11-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Behavioral Neuroscience |
| spelling | doaj.art-7787825084824f3493f07bd5c1b8cd292023-11-11T21:58:40ZengFrontiers Media S.A.Frontiers in Behavioral Neuroscience1662-51532023-11-011710.3389/fnbeh.2023.12885091288509CHL1 depletion affects dopamine receptor D2-dependent modulation of mouse behaviorLuciana Fernandes0Ralf Kleene1Ludovica Congiu2Sandra Freitag3Matthias Kneussel4Gabriele Loers5Melitta Schachner6Zentrum für Molekulare Neurobiologie, Universitätsklinikum Hamburg-Eppendorf, Hamburg, GermanyZentrum für Molekulare Neurobiologie, Universitätsklinikum Hamburg-Eppendorf, Hamburg, GermanyZentrum für Molekulare Neurobiologie, Universitätsklinikum Hamburg-Eppendorf, Hamburg, GermanyInstitut für Molekulare Neurogenetik, Zentrum für Molekulare Neurobiologie Hamburg, ZMNH, Universitätsklinikum Hamburg-Eppendorf, Hamburg, GermanyInstitut für Molekulare Neurogenetik, Zentrum für Molekulare Neurobiologie Hamburg, ZMNH, Universitätsklinikum Hamburg-Eppendorf, Hamburg, GermanyZentrum für Molekulare Neurobiologie, Universitätsklinikum Hamburg-Eppendorf, Hamburg, GermanyDepartment of Cell Biology and Neuroscience, Keck Center for Collaborative Neuroscience, Rutgers University, Piscataway, NJ, United StatesIntroductionThe dopaminergic system plays a key role in the appropriate functioning of the central nervous system, where it is essential for emotional balance, arousal, reward, and motor control. The cell adhesion molecule close homolog of L1 (CHL1) contributes to dopaminergic system development, and CHL1 and the dopamine receptor D2 (D2R) are associated with mental disorders like schizophrenia, addiction, autism spectrum disorder and depression.MethodsHere, we investigated how the interplay between CHL1 and D2R affects the behavior of young adult male and female wild-type (CHL+/+) and CHL1-deficient (CHL1−/−) mice, when D2R agonist quinpirole and antagonist sulpiride are applied.ResultsLow doses of quinpirole (0.02 mg/kg body weight) induced hypolocomotion of CHL1+/+ and CHL1−/− males and females, but led to a delayed response in CHL1−/− mice. Sulpiride (1 mg/kg body weight) affected locomotion of CHL1−/− females and social interaction of CHL1+/+ females as well as social interactions of CHL1−/− and CHL1+/+ males. Quinpirole increased novelty-seeking behavior of CHL1−/− males compared to CHL1+/+ males. Vehicle-treated CHL1−/− males and females showed enhanced working memory and reduced stress-related behavior.DiscussionWe propose that CHL1 regulates D2R-dependent functions in vivo. Deficiency of CHL1 leads to abnormal locomotor activity and emotionality, and to sex-dependent behavioral differences.https://www.frontiersin.org/articles/10.3389/fnbeh.2023.1288509/fullclose homolog of L1CHL1dopaminedopamine receptor D2behaviorquinpirole |
| spellingShingle | Luciana Fernandes Ralf Kleene Ludovica Congiu Sandra Freitag Matthias Kneussel Gabriele Loers Melitta Schachner CHL1 depletion affects dopamine receptor D2-dependent modulation of mouse behavior Frontiers in Behavioral Neuroscience close homolog of L1 CHL1 dopamine dopamine receptor D2 behavior quinpirole |
| title | CHL1 depletion affects dopamine receptor D2-dependent modulation of mouse behavior |
| title_full | CHL1 depletion affects dopamine receptor D2-dependent modulation of mouse behavior |
| title_fullStr | CHL1 depletion affects dopamine receptor D2-dependent modulation of mouse behavior |
| title_full_unstemmed | CHL1 depletion affects dopamine receptor D2-dependent modulation of mouse behavior |
| title_short | CHL1 depletion affects dopamine receptor D2-dependent modulation of mouse behavior |
| title_sort | chl1 depletion affects dopamine receptor d2 dependent modulation of mouse behavior |
| topic | close homolog of L1 CHL1 dopamine dopamine receptor D2 behavior quinpirole |
| url | https://www.frontiersin.org/articles/10.3389/fnbeh.2023.1288509/full |
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