Reduced anxiety-like and cognitive performance in mice lacking the corticotropin-releasing factor receptor 1
by
Contarino A, Dellu F, Koob GF, Smith GW, Lee KF, Vale W, Gold LH
The Scripps Research Institute,
Department of Neuropharmacology,
10550 N. Torrey Pines Road,
La Jolla, CA 92037, USA.
Brain Res 1999 Jul 17; 835(1):1-9

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.

CRF
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Antalarmin
21st century
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Ketoconazole
Sigma ligands
Cortisol blues
Drugs and reward
CRH-R antagonists
Learned helpless rats
CRF and drug addiction
Anxiety and depression
Sedatives and anxiolytics
Glucocorticoids and mood
Antidepressants and cell growth
Coricotropin-releasing hormone/depression
The immune system, depression and antidepressants
Stress, dynorphin, dysphoria and the kappa opioid system

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