Cannabinoid type 1 receptors located on single-minded 1-expressing neurons control emotional behaviors.
Neuroscience. 2012-03-01; 204: 230-244
DOI: 10.1016/j.neuroscience.2011.08.049
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1. Neuroscience. 2012 Mar 1;204:230-44. doi: 10.1016/j.neuroscience.2011.08.049.
Epub 2011 Sep 3.
Cannabinoid type 1 receptors located on single-minded 1-expressing neurons
control emotional behaviors.
Dubreucq S(1), Kambire S, Conforzi M, Metna-Laurent M, Cannich A, Soria-Gomez E,
Richard E, Marsicano G, Chaouloff F.
Author information:
(1)NeuroCentre INSERM U862, 33077 Bordeaux, France.
This study has investigated the role of hypothalamic and amygdalar type-1
cannabinoid (CB1) receptors in the emotional and neuroendocrine responses to
stress. To do so, we used the Cre/loxP system to generate conditional mutant mice
lacking the CB1 gene in neurons expressing the transcription factor single-minded
1 (Sim1). This choice was dictated by former evidence for Sim1-Cre transgenic
mice bearing Cre activity in all areas expressing Sim1, which chiefly includes
the hypothalamus (especially the paraventricular nucleus, the supraoptic nucleus,
and the posterior hypothalamus) and the mediobasal amygdala. Genomic DNA analyses
in Sim1-CB1(-/-) mice indicated that the CB1 allele was excised from the
hypothalamus and the amygdala, but not from the cortex, the striatum, the
thalamus, the nucleus accumbens, the brainstem, the hippocampus, the pituitary
gland, and the spinal cord. Double-fluorescent in situ hybridization experiments
further indicated that Sim1-CB1(-/-) mice displayed a weaker CB1 receptor mRNA
expression in the paraventricular nucleus of the hypothalamus and the mediobasal
part of the amygdala, compared to wild-type animals. Individually housed
Sim1-CB1(-/-) mice and their Sim1-CB1(+/+) littermates were exposed to anxiety
and fear memory tests under basal conditions as well as after acute/repeated
social stress. A principal component analysis of the behaviors of Sim1-CB1(-/-)
and Sim1-CB1(+/+) mice in anxiety tests (open field, elevated plus-maze, and
light/dark box) revealed that CB1 receptors from Sim1-expressing neurons exert
tonic, albeit opposite, controls of locomotor and anxiety reactivity to novel
environments. No difference between genotypes was observed during the recall of
contextual fear conditioning or during active avoidance learning. Sim1-CB1(-/-),
but not Sim1-CB1(+/+), mice proved sensitive to an acute social stress as this
procedure reverted the increased ambulation in the center of the open field. The
stimulatory influence of repeated social stress on body and adrenal weights,
water intake, and sucrose preference was similar in the two genotypes. On the
other hand, repeated social stress abolished the decrease in cued-fear
conditioned expression that was observed in Sim1-CB1(-/-) mice, compared to
Sim1-CB1(+/+) mice. This study suggests that CB1 receptors located on
Sim1-expressing neurons exert a tonic control on locomotor reactivity,
unconditioned anxiety, and cued-fear expression under basal conditions as well as
after acute or repeated stress.
Copyright © 2011 IBRO. Published by Elsevier Ltd. All rights reserved.
DOI: 10.1016/j.neuroscience.2011.08.049
PMID: 21920410 [Indexed for MEDLINE]