Department of Anesthesiology, Medical College of Wisconsin and Department of Veterans Affairs Medical Center, Milwaukee, Wisconsin 53295, USA.
Am J Physiol Regul Integr Comp Physiol. 2011 Dec;301(6):R1765-72. doi: 10.1152/ajpregu.00398.2011. Epub 2011 Sep 21.
Sympathoexcitation and increased blood pressure evoked by central networks integrating defensive behavior are fundamental to the acute stress response. A balance between excitatory glutamatergic and inhibitory GABAergic neurotransmission in the dorsal periaqueductal gray (dPAG) results in a tonic level of activity in the alerting system. Neuromodulators such as endocannabinoids have been shown to influence the sympathoexcitatory and pressor components of acute stress in the dPAG, exemplified by the defense response as a model, but the mechanism of integration remains unknown. The present study examines the role of GABA and its interaction with endocannabinoids in modulating sympathetic nerve activity and blood pressure related to the defense response. Microinjection of the broad-spectrum excitatory amino acid dl-homocysteic acid (DLH) identified sites of the defense pathway in the dPAG from which an increase in renal sympathetic nerve activity and blood pressure could be evoked, and subsequent microinjections were made at the same site through a multibarrelled micropipette. Blockade of GABAA receptors or microinjection of the cannabinoid 1 receptor agonist anandamide elicited a renal sympathoexcitation and pressor response. Prior microinjection of the GABAA receptor antagonist gabazine attenuated the sympathoexcitation and pressor response associated with anandamide microinjection. In contrast, the sympathetic response to DLH was enhanced by GABAA receptor blockade. These data demonstrate that sympathoexcitatory neurons in the dPAG are under tonic inhibition by GABA and that endocannabinoids modulate this GABAergic neurotransmission to help regulate components of the defense response.
中枢网络整合防御行为引起的交感兴奋和血压升高是急性应激反应的基础。背侧periaqueductal 灰色（dPAG）中兴奋性谷氨酸能和抑制性 GABA 能神经递质之间的平衡导致警觉系统产生紧张水平的活动。内源性大麻素等神经调质已被证明会影响 dPAG 中急性应激的交感兴奋和升压成分，以防御反应为例，但整合机制仍不清楚。本研究检查了 GABA 及其与内源性大麻素相互作用在调节与防御反应相关的交感神经活动和血压中的作用。广泛的兴奋性氨基酸 dl-高半胱氨酸（DLH）的微注射确定了 dPAG 中防御途径的部位，从这些部位可以引发肾交感神经活动和血压的增加，并且随后通过多桶微吸管在同一部位进行微注射。GABAA 受体阻断或大麻素 1 受体激动剂大麻素激动剂的微注射引起肾交感神经兴奋和升压反应。预先微注射 GABAA 受体拮抗剂gabazine 可减弱与大麻素微注射相关的交感神经兴奋和升压反应。相比之下，GABAA 受体阻断增强了对 DLH 的交感反应。这些数据表明，dPAG 中的交感兴奋神经元受到 GABA 的紧张性抑制，内源性大麻素调节这种 GABA 能神经传递以帮助调节防御反应的成分。
