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Cerebral Cortex Advance Access published online on May 13, 2008
Cerebral Cortex, doi:10.1093/cercor/bhn075
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© The Author 2008. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oxfordjournals.org

The Role of Prefrontal Cortex CB1 Receptors in the Modulation of Fear Memory

Hui-Ching Lin, Sheng-Chun Mao, Chun-Lin Su and Po-Wu Gean

Institute of Basic Medical Sciences and Department of Pharmacology, Center for Gene Regulation and Signal Transduction Research, National Cheng-Kung University, Tainan 701, Taiwan

Address correspondence to Dr Po-Wu Gean, Department of Pharmacology, College of Medicine, National Cheng-Kung University, Tainan 701, Taiwan. Email: powu{at}mail.ncku.edu.tw.

Understanding the mechanism of how fear memory can be extinguished could provide potential therapeutic strategies for the treatment of posttraumatic stress disorders. Here we show that infusion of CB1 receptor antagonist into the infralimbic (IL) subregion of the medial prefrontal cortex (mPFC) retarded cue-alone–induced reduction of fear-potentiated startle. Conversely, cannabinoid agonist WIN55212-2 (WIN) facilitated the extinction. Unexpectedly, administration of WIN without cue-alone trials reduced startle potentiation in a dose-dependent manner. The effect of cannabinoid agonists was mimicked by endocannabinoid uptake or fatty acid amide hydrolase inhibitors. Rats were trained with 10 conditioned stimulus (CS+) (yellow light)–shock pairings. Extinction training with CS+ (yellow light)-alone but not CS– (blue light)-alone trials decreased fear-potentiated startle. Intra-IL infusion of WIN before CS–-alone trials decreased startle potentiation, suggesting that the cannabinoid agonist decreased conditioned fear irrespective of whether the rats underwent CS+- or CS–-alone trials. Cannabinoid agonists activated extracellular signal-regulated kinases (ERKs) in mPFC slices, and ERK inhibitor blocked the effect of cannabinoid agonists on fear-potentiated startle. These results suggest that CB1 receptors acting through the phosphorylation of ERK are involved not only in the extinction of conditioned fear but also in the adaptation to aversive situations in general.

Key Words: CB1 receptor • extinction • fear conditioning • learning and memory • prefrontal cortex


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 Learn. Mem.Home page
H.-C. Lin, S.-C. Mao, P.-S. Chen, and P.-W. Gean
Chronic cannabinoid administration in vivo compromises extinction of fear memory
Learn. Mem., December 2, 2008; 15(12): 876 - 884.
[Abstract] [Full Text] [PDF]


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