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Abstract：
The endocannabinoid neurotransmission acting via local CB1 receptor in the bed nucleus of the stria terminalis (BNST) has been implicated in behavioral and physiological responses to emotional stress. However, the neural network related to this control is poorly understood. In this sense, the lateral hypothalamus (LH) is involved in stress responses, and BNST GABAergic neurons densely innervate this hypothalamic nucleus. However, a role of BNST projections to the LH in physiological responses to stress is unknown. Therefore, using male rats, we investigated the role of LH GABAergic neurotransmission in the regulation of cardiovascular responses to stress by CB1 receptors within the BNST. We observed that microinjection of the selective CB1 receptor antagonist AM251 into the BNST decreased the number of Fos-immunoreactive cells within the LH of rats submitted to acute restraint stress. Treatment of the BNST with AM251 also enhanced restraint-evoked tachycardia. Nevertheless, arterial pressure increase and sympathetically-mediated cutaneous vasoconstriction to restraint was not affected by CB1 receptor antagonism within the BNST. The effect of AM251 in the BNST on restraint-evoked tachycardia was abolished in animals pretreated with the selective GABAA receptor antagonist SR95531 in the LH. These results indicate that regulation of cardiovascular responses to stress by CB1 receptors in the BNST is mediated by GABAergic neurotransmission in the LH. Present data also provide evidence of the BNST endocannabinoid neurotransmission as a mechanism involved in LH neuronal activation during stressful events.
摘要：
内源性大麻素神经传递通过末端纹状体（BNST）床核中的局部CB1受体起作用，与对情绪压力的行为和生理反应有关。然而,与这种控制相关的神经网络知之甚少。在这个意义上,外侧下丘脑（LH）参与应激反应，BNSTGABA能神经元密集地支配下丘脑核。然而,BNST投射对LH在应激反应中的作用尚不清楚。因此,用雄性老鼠,我们研究了LHGABA能神经传递在调节BNST内CB1受体对应激反应的心血管反应中的作用。我们观察到，向BNST中微量注射选择性CB1受体拮抗剂AM251可减少遭受急性束缚应激的大鼠LH中Fos免疫反应性细胞的数量。用AM251治疗BNST也增强了束缚诱发的心动过速。然而，BNST内的CB1受体拮抗作用不影响动脉压升高和交感神经介导的皮肤血管收缩。在LH中用选择性GABAA受体拮抗剂SR95531预处理的动物中，BNST中AM251对束缚诱发的心动过速的作用被消除。这些结果表明，BNST中CB1受体对压力的心血管反应的调节是由LH中的GABA能神经传递介导的。目前的数据还提供了BNST内源性大麻素神经传递作为应激事件期间参与LH神经元激活的机制的证据。
