The Endocannabinoid System Differentially Regulates Escape Behavior in Mice

Frontiers in Behavioral Neuroscience
Andreas J Genewsky, C T Wotjak

Abstract

Among the hardwired behaviors, fear or survival responses certainly belong to the most evolutionary conserved ones. However, higher animals possess the ability to adapt to certain environments (e.g., novel foraging grounds), and, therefore, those responses need to be plastic. Previous studies revealed a cell-type specific role of the endocannabinoid system in novelty fear, conditioned fear and active vs. passive avoidance in a shuttle box paradigm. In this study we aim to investigate, whether knocking-out the cannabinoid receptor type-1 (CB1) on cortical glutamatergic (Glu-CB1(-/-)) or GABAergic (GABA-CB1(-/-)) neurons differentially affects the level of behavioral inhibition, which could ultimately lead to differences in escape behavior. In this context, we developed a novel behavioral paradigm, the Moving Wall Box (MWB). Using the MWB task we could show that Glu-CB1(-/-) mice have higher levels of behavioral inhibition over the course of repeated testing. GABA-CB1(-/-) mice, in contrast, showed significantly lower levels of behavioral inhibition compared to wild-type controls and more escape behavior. These changes in behavioral inhibition and escape behavior cannot be explained by altered levels of arousal, as repeated start...Continue Reading

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