The endocannabinoid (eCB) system regulates emotion, stress, memory and cognition through the CB₁ receptor. In order to test the role of CB₁ signaling in social anxiety and memory, we utilized a genetic knockout (KO) and a pharmacological approach. Specifically, we assessed the effects of a constitutive KO of CB₁ receptors (CB₁ KOs) and systemic administration of a CB₁antagonist (AM251; 5 mg/kg) on social anxiety in a social investigation paradigm and social memory in a social discrimination test. Results showed that when compared to wildtypes (WT) and vehicle-treated animals, CB₁ KOs and WT animals that received an acute dose of AM251 displayed anxiety-like behaviors toward a novel male conspecific. When compared to WT animals, KOs showed both active and passive defensive coping behaviors; i.e. elevated avoidance, freezing and risk-assessment behaviors, all consistent with an anxiety-like profile. Animals that received acute doses of AM251 also showed an anxiety-like profile when compared to vehicle treated animals, yet did not show an active coping strategy i.e. changes in risk-assessment behaviors. In the social discrimination test, CB₁ KOs and animals that received the CB₁ antagonist showed enhanced levels of social memory relative to their respective controls. These results clearly implicate CB₁ receptors in the regulation of social anxiety, memory and arousal. The elevated arousal/ anxiety resulting from either total CB₁ deletion or an acute CB₁ blockade may promote enhanced social discrimination/memory. These findings may emphasize the role of the eCB system in anxiety and memory to affect social behavior.
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PMID:

 

23647582

 

[PubMed – as supplied by publisher]

http://www.ncbi.nlm.nih.gov/pubmed/23647582