CB1 receptors in corticotropin-releasing factor neurons selectively control the acoustic startle response in male mice.

Autor: Ruat J; Department Stress Neurobiology and Neurogenetics, Max Planck Institute of Psychiatry, Munich, Germany.; International Max Planck Research School for Translational Psychiatry (IMPRS-TP), Max Planck Institute of Psychiatry, Munich, Germany.; Research Group Neuronal Plasticity, Max Planck Institute of Psychiatry, Munich, Germany., Hartmann A; Research Group Neuronal Plasticity, Max Planck Institute of Psychiatry, Munich, Germany., Heinz DE; Research Group Neuronal Plasticity, Max Planck Institute of Psychiatry, Munich, Germany.; Max Planck School of Cognition, Max Planck Institute for Human Cognitive and Brain Sciences, Leipzig, Germany., Nemcova P; Research Group Neuronal Plasticity, Max Planck Institute of Psychiatry, Munich, Germany., Stoffel R; Department Stress Neurobiology and Neurogenetics, Max Planck Institute of Psychiatry, Munich, Germany., Deussing JM; Research Group Molecular Neurogenetics, Max Planck Institute of Psychiatry, Munich, Germany.; Scientific Core Unit Genetically Engineered Mouse Models, Max Planck Institute of Psychiatry, Munich, Germany., Chen A; Department Stress Neurobiology and Neurogenetics, Max Planck Institute of Psychiatry, Munich, Germany.; Department of Neurobiology, Weizmann Institute of Science, Rehovot, Israel., Wotjak CT; Research Group Neuronal Plasticity, Max Planck Institute of Psychiatry, Munich, Germany.; Max Planck School of Cognition, Max Planck Institute for Human Cognitive and Brain Sciences, Leipzig, Germany.; Central Nervous System Diseases Research (CNSDR), Boehringer Ingelheim Pharma GmbH & Co KG, Biberach an der Riss, Germany.
Jazyk: angličtina
Zdroj: Genes, brain, and behavior [Genes Brain Behav] 2021 Nov; Vol. 20 (8), pp. e12775. Date of Electronic Publication: 2021 Oct 21.
DOI: 10.1111/gbb.12775
Abstrakt: The endocannabinoid system is an important regulator of the hormonal and behavioral stress responses, which critically involve corticotropin-releasing factor (CRF) and its receptors. While it has been shown that CRF and the cannabinoid type 1 (CB1) receptor are co-localized in several brain regions, the physiological relevance of this co-expression remains unclear. Using double in situ hybridization, we confirmed co-localization in the piriform cortex, the lateral hypothalamic area, the paraventricular nucleus, and the Barrington's nucleus, albeit at low levels. To study the behavioral and physiological implications of this co-expression, we generated a conditional knockout mouse line that selectively lacks the expression of CB1 receptors in CRF neurons. We found no effects on fear and anxiety-related behaviors under basal conditions nor after a traumatic experience. Additionally, plasma corticosterone levels were unaffected at baseline and after restraint stress. Only acoustic startle responses were significantly enhanced in male, but not female, knockout mice. Taken together, the consequences of depleting CB1 in CRF-positive neurons caused a confined hyperarousal phenotype in a sex-dependent manner. The current results suggest that the important interplay between the central endocannabinoid and CRF systems in regulating the organism's stress response is predominantly taking place at the level of CRF receptor-expressing neurons.
(© 2021 The Authors. Genes, Brain and Behavior published by International Behavioural and Neural Genetics Society and John Wiley & Sons Ltd.)
Databáze: MEDLINE
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