Antidepressant-like behavioral effects of impaired cannabinoid receptor type 1 signaling coincide with exaggerated corticosterone secretion in mice.
Psychoneuroendocrinology. 2008-01-01; 33(1): 54-67
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1. Psychoneuroendocrinology. 2008 Jan;33(1):54-67. Epub 2007 Oct 31.
Antidepressant-like behavioral effects of impaired cannabinoid receptor type 1
signaling coincide with exaggerated corticosterone secretion in mice.
Steiner MA(1), Marsicano G, Nestler EJ, Holsboer F, Lutz B, Wotjak CT.
(1)Max Planck Institute of Psychiatry, Kraepelinstrasse 2-10, 80804 Munich,
Hypothalamic-pituitary-adrenocortical (HPA) axis hyperactivity is associated with
major depressive disorders, and treatment with classical antidepressants
ameliorates not only psychopathological symptoms, but also the dysregulation of
the HPA axis. Here, we further elucidated the role of impaired cannabinoid type 1
receptor (CB1) signaling for neuroendocrine and behavioral stress coping in the
mouse forced swim test (FST). We demonstrate that the genetic inactivation of CB1
is accompanied by increased plasma corticosterone levels both under basal
conditions and at different time points following exposure to the FST. The latter
effect could be mimicked in C57BL/6N mice by acute, subchronic, and chronic
administration of the selective CB1 antagonist SR141716. Further experiments
confirmed the specificity of corticosterone-elevating SR141716 actions for CB1 in
CB1-deficient mice. Subchronic and chronic pharmacological blockade of CB1, but
not its genetic deletion, induced antidepressant-like behavioral responses in the
FST that were characterized by decreased floating and/or increased struggling
behavior. The antidepressant-like behavioral effects of acute desipramine
treatment in the FST were absent in CB1-deficient mice, but the dampening effects
of desipramine on FST stress-induced corticosterone secretion were not
compromised by CB1 deficiency. However, antidepressant-like behavioral
desipramine effects were intact in C57BL/6N mice pre-treated with SR141716,
indicating potential developmental deficits in CB1-deficient mice. We conclude
that pharmacological blockade of CB1 signaling shares antidepressant-like
behavioral effects with desipramine, but reveals opposite effects on HPA axis
PMID: 17976922 [Indexed for MEDLINE]