Inglefield J R, Kellogg C K
Department of Neurobiology and Anatomy, University of Rochester, New York 14642.
Psychopharmacology (Berl). 1994 Nov;116(3):339-45. doi: 10.1007/BF02245338.
Pharmacologic blockade of GABA binding sites in the hypothalamus elicits a pattern of physiological and behavioral arousal. The latter outcome implicates a perturbation in the neural functioning of higher brain centers. The effect that hypothalamic GABAA receptor modulation has on the function of cerebral cortical neural substrates linked with responses to stressors was assessed using microinfusion of bicuculline methiodide (BMI) into the medial hypothalamus of freely moving, handling habituated rats. BMI led to rapid increases in frontal cortical dopamine (DA) utilization (calculated from the sum of the levels of the DA metabolites, homovanilic and dihydroxyphenylacetic acids, divided by DA levels) resembling that identified following restraint-induced stress. Also, cortical GABAA receptor function [using chloride (Cl-) enhancement of 3H-flunitrazepam (Flu) binding as an index] was disrupted; i.e. there was a loss of typical Cl- enhancement of 3H-Flu binding in animals after BMI infusions. However, placing animals in restraint after BMI infusion reversed the effects of BMI, with both DA utilization and Cl- facilitated 3H-Flu binding similar to control basal values. Muscimol infusions in separately prepared animals did not alter either frontal cortical DA utilization or GABAA receptor function. The present results implicate GABA in the hypothalamus as "gating" activity of cortical systems involved in sensation of and/or responses to stressors. These findings may have important implications for effects of autonomic arousal on neural substrates involved in mediating stress responses.
下丘脑γ-氨基丁酸（GABA）结合位点的药理学阻断引发了一种生理和行为唤醒模式。后一种结果暗示了高等脑中枢神经功能的紊乱。利用向自由活动、习惯处理的大鼠内侧下丘脑微量注射甲磺酸荷包牡丹碱（BMI），评估下丘脑GABAA受体调节对与应激源反应相关的大脑皮质神经底物功能的影响。BMI导致额叶皮质多巴胺（DA）利用率迅速增加（根据DA代谢物高香草酸和二羟基苯乙酸水平之和除以DA水平计算），类似于束缚诱导应激后观察到的情况。此外，皮质GABAA受体功能[以氯化物（Cl-）增强3H-氟硝西泮（Flu）结合为指标]受到破坏；即BMI注射后动物中3H-Flu结合的典型Cl-增强作用丧失。然而，在BMI注射后对动物进行束缚可逆转BMI的作用，DA利用率和Cl-促进的3H-Flu结合均类似于对照基础值。在单独制备的动物中注射蝇蕈醇既不改变额叶皮质DA利用率，也不改变GABAA受体功能。目前的结果表明，下丘脑GABA作为参与应激源感知和/或反应的皮质系统的“门控”活动。这些发现可能对自主唤醒对介导应激反应的神经底物的影响具有重要意义。
