Smith R D, Turek F W, Slater N T
Department of Neurobiology and Physiology, Northwestern University, Evanston, IL 60208.
Brain Res. 1990 Oct 22;530(2):275-82. doi: 10.1016/0006-8993(90)91295-r.
Permanent phase shifts in the free-running rhythm of locomotor activity of the golden hamster were induced with microinjections of the gamma-aminobutyric acid (GABA) agonists muscimol or baclofen in the hypothalamic suprachiasmatic nuclei. Muscimol and baclofen exhibit relatively high binding affinities for GABAA and GABAB receptors, respectively. Microinjections of the GABA antagonists, bicuculline methobromide or picrotoxinin, thought to block the actions of GABA at GABAA receptors, could block phase shifts induced by muscimol but not the benzodiazepine, triazolam. Microinjections of the postsynaptic GABAB receptor antagonist phaclofen, which blocks the actions of GABA at postsynaptic but not at presynaptic GABAB receptor sites, did not block the phase-shifting actions of either muscimol or baclofen. GABAergic antagonists when given alone did not induce phase shifts. Collectively, these studies indicate that when activated by exogenous GABAergic agents, a GABAergic system associated with both GABAA and GABAB receptors exists as a neural regulatory mechanism that can reset the mammalian circadian clock. However, GABAergic synaptic pathways may not be normally involved in the circadian timing system.
通过向金黄仓鼠下丘脑视交叉上核微量注射γ-氨基丁酸（GABA）激动剂蝇蕈醇或巴氯芬，可诱导其运动活动的自由运行节律发生永久性相位偏移。蝇蕈醇和巴氯芬分别对GABAA和GABAB受体表现出相对较高的结合亲和力。微量注射GABA拮抗剂甲溴东莨菪碱或印防己毒素（据认为可阻断GABA在GABAA受体上的作用），可阻断蝇蕈醇诱导的相位偏移，但不能阻断苯二氮䓬类药物三唑仑诱导的相位偏移。微量注射突触后GABAB受体拮抗剂巴氯芬（可阻断GABA在突触后而非突触前GABAB受体位点的作用），不能阻断蝇蕈醇或巴氯芬的相位偏移作用。单独给予GABA能拮抗剂不会诱导相位偏移。总体而言，这些研究表明，当被外源性GABA能药物激活时，与GABAA和GABAB受体相关的GABA能系统作为一种神经调节机制存在，可重置哺乳动物的生物钟。然而，GABA能突触通路可能通常不参与昼夜节律计时系统。
