Bimodal control of fear-coping strategies by CB₁ cannabinoid receptors.
Journal of Neuroscience. 2012-05-23; 32(21): 7109-7118
DOI: 10.1523/jneurosci.1054-12.2012
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1. J Neurosci. 2012 May 23;32(21):7109-18. doi: 10.1523/JNEUROSCI.1054-12.2012.
Bimodal control of fear-coping strategies by CB₁ cannabinoid receptors.
Metna-Laurent M(1), Soria-Gómez E, Verrier D, Conforzi M, Jégo P, Lafenêtre P,
Marsicano G.
Author information:
(1)INSERM U862, NeuroCentre Magendie, 33076 Bordeaux, France.
To maximize their chances of survival, animals need to rapidly and efficiently
respond to aversive situations. These responses can be classified as active or
passive and depend on the specific nature of threats, but also on individual fear
coping styles. In this study, we show that the control of excitatory and
inhibitory brain neurons by type-1 cannabinoid (CB₁) receptors is a key
determinant of fear coping strategies in mice. In classical fear conditioning, a
switch between initially predominant passive fear responses (freezing) and active
behaviors (escape attempts and risk assessment) develops over time. Constitutive
genetic deletion of CB₁ receptors in CB₁⁻/⁻ mice disrupted this pattern by
favoring passive responses. This phenotype can be ascribed to endocannabinoid
control of excitatory neurons, because it was reproduced in conditional mutant
mice lacking CB₁ receptors from cortical glutamatergic neurons. CB₁ receptor
deletion from GABAergic brain neurons led to the opposite phenotype,
characterized by the predominance of active coping. The CB₁ receptor agonist
Δ⁹-tetrahydrocannabinol exerted a biphasic control of fear coping strategies,
with lower and higher doses favoring active and passive responses, respectively.
Finally, viral re-expression of CB₁ receptors in the amygdala of CB₁⁻/⁻ mice
restored the normal switch between the two coping strategies. These data strongly
suggest that CB₁ receptor signaling bimodally controls the spontaneous adoption
of active or passive coping strategies in individuals. This primary function of
the endocannabinoid system in shaping individual behavioral traits should be
considered when studying the mechanisms of physiological and pathological fear.
DOI: 10.1523/JNEUROSCI.1054-12.2012
PMID: 22623656 [Indexed for MEDLINE]