1 research outputs found
Bimodal control of fear-coping strategies by CBâ cannabinoid receptors
International audienceTo 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 (CBâ) 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 CBâ receptors in CBââ»/â» 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 CBâ receptors from cortical glutamatergic neurons. CBâ receptor deletion from GABAergic brain neurons led to the opposite phenotype, characterized by the predominance of active coping. The CBâ receptor agonist Îâč-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 CBâ receptors in the amygdala of CBââ»/â» mice restored the normal switch between the two coping strategies. These data strongly suggest that CBâ 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