Cannabinoid Control of Fear Responses

Abstract

In 2002, a landmark study showed that the endogenous activity of the cannabinoid type-1 (CB 1 ) receptors is necessary for extinction of conditioned freezing in mice (Marsicano G, Wotjak CT, Azad SC, Bisogno T, Rammes G, Cascio MG, Hermann H, Tang J, Hofmann C, Zieglgänsberger W, Di Marzo V, Lutz B. The endogenous cannabinoid system controls extinction of aversive memories. Nature. 2002 Aug 1;418(6897):530-4.). Since extinction of conditioned freezing is an important indicator of fear adaptation in animals and because our ability to control emotional responses is important to ensure adapted behaviors, the potential function of the endocannabinoid system (ECS) in such processes has generated a large interest. In this chapter, we will provide pieces of information linking the activity of the ECS and fear modulation.

Addressing sufficiency of the CB1 receptor for endocannabinoid-mediated functions through conditional genetic rescue in forebrain GABAergic neurons

“…The endocannabinoid system serves many functions and is involved in the regulation of numerous processes. These include seizure susceptibility (e.g., Soltesz et al 2015 ) and both innate and learned fear or anxiety (e.g., Ruehle et al 2012 ; Aliczki and Haller 2015 ; Metna-Laurent et al 2015 ; Lutz et al 2015 ). Considering that the CB1 receptor is expressed, among others, in both glutamatergic and GABAergic neurons (Marsicano and Lutz 1999 ), many efforts have been made to dissect the specific involvement of the receptor in these two neuronal subpopulations in different endocannabinoid functions.…”