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Updated: Mar 22, 2026
Trace Fear Conditioning in Mice
Published on: March 20, 2014
FAAH inhibitor OL-135 disrupts contextual, but not auditory, fear conditioning in rats
Michael A Burman1, Kerribeth Szolusha1, Rebecca Bind2
1Department of Psychology, United States; Center for Excellence in the Neurosciences, University of New England, United States.
Abstract:
Anxiety disorders are among the most prevalent psychological disorders, have significant negative impacts on quality of life and the healthcare system, and yet effective treatments remain elusive. Manipulating the endocannabinoid system has demonstrated potential for treating anxiety, although the side effects of direct manipulations of cannabinoid receptors keeps them from widespread clinical use. Disrupting the degradation enzyme fatty acid amide hydrolase (FAAH) enhances endogenous signaling and may produce similar efficacy without the side effects. The current experiments examine the effects of low (5.6mg/kg) or moderate (10.0mg/kg) doses of OL-135, a FAAH inhibitor, on the acquisition and consolidation of classical fear conditioning, a common model of trauma-induced anxiety. The acquisition of contextual, but not auditory, fear conditioning was disrupted by both doses of OL-135. Shock reactivity was not affected. Due to the additional neural circuitry required for contextual, but not auditory, fear conditioning, these data suggest that endocannabinoid signaling outside the amygdala may be critical for a subset of fearful memories.
Insights
Inhibiting fatty acid amide hydrolase (FAAH) with OL-135 disrupted contextual fear memory acquisition in a preclinical model. This suggests targeting FAAH may offer a novel therapeutic strategy for anxiety disorders.
Area of Science:
- Neuroscience
- Pharmacology
- Psychology
Background:
- Anxiety disorders are prevalent, impacting quality of life and healthcare, with limited effective treatments.
- The endocannabinoid system shows promise for anxiety treatment, but direct cannabinoid receptor manipulation has side effects.
- Inhibiting fatty acid amide hydrolase (FAAH) enhances endogenous cannabinoid signaling, potentially offering a safer therapeutic approach.
Purpose of the Study:
- To investigate the effects of the FAAH inhibitor OL-135 on fear memory.
- To determine if OL-135 impacts the acquisition and consolidation of classical fear conditioning.
Main Methods:
- Experiments utilized classical fear conditioning, a model for trauma-induced anxiety.
- Rats were administered low (5.6mg/kg) or moderate (10.0mg/kg) doses of OL-135.
- The study assessed the acquisition and consolidation of contextual and auditory fear conditioning, as well as shock reactivity.
Main Results:
- Both doses of OL-135 significantly disrupted the acquisition of contextual fear conditioning.
- Auditory fear conditioning acquisition and shock reactivity were not affected by OL-135.
- These findings indicate a specific effect of FAAH inhibition on certain types of fear memory.
Conclusions:
- Endocannabinoid signaling, modulated by FAAH, plays a critical role in the acquisition of contextual fear memories.
- Targeting FAAH may be a viable strategy for treating specific aspects of anxiety disorders, potentially avoiding side effects associated with direct cannabinoid receptor agonists.
- These results suggest that endocannabinoid signaling outside the amygdala is crucial for certain fearful memories.
