Endocannabinoids mediate acute fear adaptation via glutamatergic neurons independently of corticotropin-releasing hormone signaling.
Genes, Brain and Behavior. 2009-03-01; 8(2): 203-211
DOI: 10.1111/j.1601-183x.2008.00463.x
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1. Genes Brain Behav. 2009 Mar;8(2):203-11. doi: 10.1111/j.1601-183X.2008.00463.x.
Epub 2008 Dec 3.
Endocannabinoids mediate acute fear adaptation via glutamatergic neurons
independently of corticotropin-releasing hormone signaling.
Kamprath K(1), Plendl W, Marsicano G, Deussing JM, Wurst W, Lutz B, Wotjak CT.
Author information:
(1)Max Planck Institute of Psychiatry, Munich, Germany.
Recent evidence showed that the endocannabinoid system plays an important role in
the behavioral adaptation of stress and fear responses. In this study, we chose a
behavioral paradigm that includes criteria of both fear and stress responses to
assess whether the involvement of endocannabinoids in these two processes rely on
common mechanisms. To this end, we delivered a footshock and measured the fear
response to a subsequently presented novel tone stimulus. First, we exposed
different groups of cannabinoid receptor type 1 (CB(1))-deficient mice (CB(1)
(-/-)) and their wild-type littermates (CB(1) (+/+)) to footshocks of different
intensities. Only application of an intense footshock resulted in a sustained
fear response to the tone in CB(1) (-/-). Using the intense protocol, we next
investigated whether endocannabinoids mediate their effects via an interplay with
corticotropin-releasing hormone (CRH) signaling. Pharmacological blockade of
CB(1) receptors by rimonabant in mice deficient for the CRH receptor type 1
(CRHR1(-/-)) or type 2 (CRHR2(-/-)), and in respective wild-type littermates,
resulted in a sustained fear response in all genotypes. This suggests that CRH is
not involved in the fear-alleviating effects of CB(1). As CRHR1(-/-) are known to
be severely impaired in stress-induced corticosterone secretion, our observation
also implicates that corticosterone is dispensable for CB(1)-mediated acute fear
adaptation. Instead, conditional mutants with a specific deletion of CB(1) in
principal neurons of the forebrain (CaMK-CB(1) (-/-)), or in cortical
glutamatergic neurons (Glu-CB(1) (-/-)), showed a similar phenotype as CB(1)
(-/-), thus indicating that endocannabinoid-controlled glutamatergic transmission
plays an essential role in acute fear adaptation.
DOI: 10.1111/j.1601-183X.2008.00463.x
PMID: 19077175 [Indexed for MEDLINE]