Laboratory of Neurobiology and Behavior; Laboratory of Neuroendocrinology, The Rockefeller University, New York, NY 10065, USA.
Genes Brain Behav. 2013 Jul;12(5):479-89. doi: 10.1111/gbb.12045. Epub 2013 May 22.
The endocannabinoid (eCB) system regulates emotion, stress, memory and cognition through the cannabinoid type 1 (CB1 ) receptor. 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 CB1 antagonist (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 with wild-type (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 with 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 with 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.
内源性大麻素（eCB）系统通过大麻素 1 型（CB1）受体调节情绪、应激、记忆和认知。为了测试 CB1 信号在社交焦虑和记忆中的作用，我们利用了基因敲除（KO）和药理学方法。具体来说，我们评估了 CB1 受体组成型敲除（CB1 KOs）和全身给予 CB1 拮抗剂（AM251；5mg/kg）对社交调查范式中的社交焦虑和社交辨别测试中的社交记忆的影响。结果表明，与野生型（WT）和载体处理动物相比，CB1 KOs 和接受 AM251 急性剂量的 WT 动物对新雄性同种动物表现出类似焦虑的行为。与 WT 动物相比，KO 表现出主动和被动防御应对行为，即回避、冻结和风险评估行为增加，所有这些都与类似焦虑的表型一致。与载体处理动物相比，接受 AM251 急性剂量的动物也表现出类似焦虑的表型，但没有表现出主动应对策略，即风险评估行为的变化。在社交辨别测试中，CB1 KOs 和接受 CB1 拮抗剂的动物与各自的对照相比，表现出增强的社交记忆水平。这些结果清楚地表明 CB1 受体在调节社交焦虑、记忆和唤醒中起作用。由于总 CB1 缺失或急性 CB1 阻断引起的唤醒/焦虑可能会促进增强的社交辨别/记忆。这些发现可能强调了内源性大麻素系统在焦虑和记忆中的作用，以影响社交行为。
