Editors' ChoiceNeurobiology

Don't Fear Cannabinoids!

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Science's STKE  06 Aug 2002:
Vol. 2002, Issue 144, pp. tw285-TW285
DOI: 10.1126/stke.2002.144.tw285

Fear-related memories often provoke certain aversive behaviors. However, through an ambiguous process called extinguishing, which may involve synaptic plasticity and N-methyl-D-aspartate (NMDA)-type receptors in the amygdala region of the brain, such associations can be weakened. Marsicano et al. propose that the process also involves endocannabinoids and cannabinoid receptor 1 (CB1), two factors previously implicated in memory processing. Mice lacking CB1 or wild-type mice treated with a CB1 antagonist could not extinguish the memory of a sound that was associated with the application of an aversive stimulus (electric shock). This conditioned fearful response was observed in wild-type mice, but was eventually extinguished. Levels of endocannabinoids increased in both mutant and normal mice, suggesting that signaling through CB1 is critical to the extinguishing process. The authors propose that endocannabinoids may reduce the release of the inhibitory neurotransmitter GABA in the amygdala.

G. Marsicano, C. T. Wotjak, S. C. Azad, T. Bisogno, G. Rammes, M. G. Cascio, H. Herman, J. Tang, C. Hofmann, W. Zieglgansberger, V. Di Marzo, B. Lutz, The endogenous cannabinoid system controls extinction of aversive memories. Nature 418, 530-534 (2002). [Online Journal]

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