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Reduced anxiety-like and cognitive performance in mice lacking the corticotropin-releasing factor receptor 1
A Contarino1, F Dellu, G F Koob
1The Scripps Research Institute, Department of Neuropharmacology, 10550 N. Torrey Pines Road, La Jolla, CA 92037, USA.
Abstract:
Corticotropin-releasing factor (CRF) has been hypothesized to be involved in the pathophysiology of anxiety, depression, cognitive and feeding disorders. Two distinct CRF receptor subtypes, CRFR1 and CRFR2, are thought to mediate CRF actions in the CNS. However, the role for each receptor subtype in animal models of neuropsychiatric disorders remains to be determined. Using CRFR1 deficient mice, the present study investigated the functional significance of this CRF receptor subtype in anxiety-like and memory processes. CRFR1 knockout mice displayed an increased exploratory behavior in both the Elevated Plus-maze (EPM) and the Black and White (B-W) test box models of anxiety, indicating an anxiolytic-like effect of the CRFR1 gene deletion. In contrast, during the retrieval trial of a two-trial spatial memory task wild type mice made more visits to and spent more time in the novel arm as opposed to the two familiar ones of a Y-maze apparatus. No increase in the level of exploration of the novel arm by the CRFR1 deficient mice was observed. This indicates that CRFR1 knockout mice are impaired in spatial recognition memory. These results demonstrate that genetic deletion of the CRFR1 receptor can lead to impairments in anxiety-like and cognitive behaviors, supporting a critical role for this receptor in anxiety and cognitive biological processes.
Insights
Genetic deletion of the Corticotropin-releasing factor receptor 1 (CRFR1) gene in mice resulted in anxiolytic-like effects and impaired spatial recognition memory, suggesting CRFR1
Area of Science:
- Neuroscience
- Behavioral Science
- Genetics
Background:
- Corticotropin-releasing factor (CRF) is implicated in anxiety, depression, cognitive, and feeding disorders.
- Two CRF receptor subtypes, CRFR1 and CRFR2, mediate CRF actions in the central nervous system (CNS).
- The specific roles of CRFR1 and CRFR2 in neuropsychiatric disorder models are not fully understood.
Purpose of the Study:
- To investigate the functional significance of the CRFR1 receptor subtype in anxiety-like and memory processes.
- To determine the behavioral effects of CRFR1 gene deletion in a mouse model.
Main Methods:
- Utilized CRFR1 deficient (knockout) mice.
- Assessed anxiety-like behaviors using the Elevated Plus-maze (EPM) and Black and White (B-W) test box.
- Evaluated spatial recognition memory using a two-trial Y-maze task.
Main Results:
- CRFR1 knockout mice exhibited increased exploratory behavior in EPM and B-W tests, indicating an anxiolytic-like effect.
- CRFR1 knockout mice showed impaired spatial recognition memory, failing to increase exploration of the novel arm in the Y-maze.
- Wild-type mice demonstrated normal novel arm exploration, confirming the memory deficit in CRFR1 deficient mice.
Conclusions:
- Genetic deletion of the CRFR1 receptor leads to anxiolytic-like behaviors.
- CRFR1 receptor deficiency results in significant impairments in spatial recognition memory.
- These findings highlight a critical role for CRFR1 in anxiety and cognitive processes.