A New Behavioral Paradigm for Frustrative Nonreward in Juvenile Mice
Background: Irritability, defined as proneness to anger, can reach a pathological extent. It is a defining symptom of disruptive mood dysregulation disorder and one of the most common reasons youths present for psychiatric evaluation and care. Aberrant responses to frustrative nonreward (FNR), the r...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2024-01-01
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| Series: | Biological Psychiatry Global Open Science |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2667174323001374 |
| _version_ | 1797598025164521472 |
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| author | Aijaz Ahmad Naik Xiaoyu Ma Maxime Munyeshyaka Ellen Leibenluft Zheng Li |
| author_facet | Aijaz Ahmad Naik Xiaoyu Ma Maxime Munyeshyaka Ellen Leibenluft Zheng Li |
| author_sort | Aijaz Ahmad Naik |
| collection | DOAJ |
| description | Background: Irritability, defined as proneness to anger, can reach a pathological extent. It is a defining symptom of disruptive mood dysregulation disorder and one of the most common reasons youths present for psychiatric evaluation and care. Aberrant responses to frustrative nonreward (FNR), the response to omission of expected reward, are central to the pathophysiology of irritability. FNR is a translational construct to study irritability across species. The development of preclinical FNR models would advance mechanistic studies of the important and relatively understudied clinical phenomenon of irritability. Methods: We used FNR as a conceptual framework to develop a novel mouse behavioral paradigm named alternate poking reward omission. Juvenile mice were exposed to alternate poking reward omission and then examined with a battery of behavioral tests to determine the behavioral effect of FNR. Results: FNR increased locomotion and aggression regardless of sex. These behavioral changes elicited by FNR resemble the symptoms observed in youth with severe irritability. FNR had no effect on anxiety-like, depression-like, or nonaggressive social behaviors. Conclusions: Our alternate poking reward omission paradigm effectively elevated aggression and locomotion in juvenile mice. These frustration effects are directly related to behavioral symptoms of youth with severe irritability. Our novel behavioral paradigm lays the groundwork for further mechanistic studies of frustration and irritability in rodents. |
| first_indexed | 2024-03-11T03:13:34Z |
| format | Article |
| id | doaj.art-859463c520ab493a95e2f761ecc94a6a |
| institution | Directory Open Access Journal |
| issn | 2667-1743 |
| language | English |
| last_indexed | 2024-03-11T03:13:34Z |
| publishDate | 2024-01-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Biological Psychiatry Global Open Science |
| spelling | doaj.art-859463c520ab493a95e2f761ecc94a6a2023-11-18T04:30:00ZengElsevierBiological Psychiatry Global Open Science2667-17432024-01-01413138A New Behavioral Paradigm for Frustrative Nonreward in Juvenile MiceAijaz Ahmad Naik0Xiaoyu Ma1Maxime Munyeshyaka2Ellen Leibenluft3Zheng Li4Section on Synapse Development Plasticity, National Institute of Mental Health, National Institutes of Health, Bethesda, Maryland; Center on Compulsive Behaviors, Intramural Research Program, National Institutes of Health, Bethesda, MarylandSection on Synapse Development Plasticity, National Institute of Mental Health, National Institutes of Health, Bethesda, MarylandSection on Synapse Development Plasticity, National Institute of Mental Health, National Institutes of Health, Bethesda, MarylandSection on Mood Dysregulation and Neuroscience, National Institute of Mental Health, National Institutes of Health, Bethesda, MarylandSection on Synapse Development Plasticity, National Institute of Mental Health, National Institutes of Health, Bethesda, Maryland; Address correspondence to Zheng Li, Ph.D.Background: Irritability, defined as proneness to anger, can reach a pathological extent. It is a defining symptom of disruptive mood dysregulation disorder and one of the most common reasons youths present for psychiatric evaluation and care. Aberrant responses to frustrative nonreward (FNR), the response to omission of expected reward, are central to the pathophysiology of irritability. FNR is a translational construct to study irritability across species. The development of preclinical FNR models would advance mechanistic studies of the important and relatively understudied clinical phenomenon of irritability. Methods: We used FNR as a conceptual framework to develop a novel mouse behavioral paradigm named alternate poking reward omission. Juvenile mice were exposed to alternate poking reward omission and then examined with a battery of behavioral tests to determine the behavioral effect of FNR. Results: FNR increased locomotion and aggression regardless of sex. These behavioral changes elicited by FNR resemble the symptoms observed in youth with severe irritability. FNR had no effect on anxiety-like, depression-like, or nonaggressive social behaviors. Conclusions: Our alternate poking reward omission paradigm effectively elevated aggression and locomotion in juvenile mice. These frustration effects are directly related to behavioral symptoms of youth with severe irritability. Our novel behavioral paradigm lays the groundwork for further mechanistic studies of frustration and irritability in rodents.http://www.sciencedirect.com/science/article/pii/S2667174323001374AggressionDMDDFrustrative nonrewardHyperlocomotionIrritability |
| spellingShingle | Aijaz Ahmad Naik Xiaoyu Ma Maxime Munyeshyaka Ellen Leibenluft Zheng Li A New Behavioral Paradigm for Frustrative Nonreward in Juvenile Mice Biological Psychiatry Global Open Science Aggression DMDD Frustrative nonreward Hyperlocomotion Irritability |
| title | A New Behavioral Paradigm for Frustrative Nonreward in Juvenile Mice |
| title_full | A New Behavioral Paradigm for Frustrative Nonreward in Juvenile Mice |
| title_fullStr | A New Behavioral Paradigm for Frustrative Nonreward in Juvenile Mice |
| title_full_unstemmed | A New Behavioral Paradigm for Frustrative Nonreward in Juvenile Mice |
| title_short | A New Behavioral Paradigm for Frustrative Nonreward in Juvenile Mice |
| title_sort | new behavioral paradigm for frustrative nonreward in juvenile mice |
| topic | Aggression DMDD Frustrative nonreward Hyperlocomotion Irritability |
| url | http://www.sciencedirect.com/science/article/pii/S2667174323001374 |
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