Nissen R, Hu B, Renaud L P
Neuroscience Unit, Loeb Research Institute, Ottawa Civic Hospital, Ontario, Canada.
Neuroscience. 1994 Mar;59(1):115-20. doi: 10.1016/0306-4522(94)90103-1.
Supraoptic neurosecretory neurons express a prominent N-methyl-D-aspartate receptor system. Recent in vitro evidence reveals that N-methyl-D-aspartate receptor activation dramatically alters the spontaneous discharge patterns of supraoptic neurons. In this study we evaluate whether N-methyl-D-aspartate receptors in vivo contribute to the development of characteristic phasic discharge patterns displayed by vasopressin-secreting neurons. Intravenous administration of ketamine hydrochloride, a non-competitive N-methyl-D-aspartate receptor antagonist, was used to examine whether N-methyl-D-aspartate receptor blockade influences patterned spontaneous discharge observed in supraoptic neurosecretory neurons. Extracellular recordings were obtained from identified hypothalamic supraoptic neurons in pentobarbital-anaesthetized Long-Evans rats. Systemic administration of ketamine (< or = 1.5 mg/kg) potently suppressed spontaneous phasic discharge in 16/19 putative vasopressin-secreting cells. The ketamine-induced blockade was dose dependent, fully reversible and was associated with the complete blockade of activity evoked by local pressure application of N-methyl-D-aspartate, but not the activity evoked by alpha-amino-3-hydroxy-5-methyl-isoxazole-4-propionate receptor agonists (6/6 cells). Ketamine had no detectable effect on threshold or shape of antidromic action potentials. By comparison, the activity in 9/10 continuously active neurons (putative oxytocin-secreting) was unaffected by administration of identical doses of ketamine. These data suggest that N-methyl-D-aspartate receptors play an important role in regulating the onset and maintenance of spontaneous phasic activity patterns displayed by rat supraoptic vasopressin neurons in vivo.
视上核神经分泌神经元表达一种显著的N-甲基-D-天冬氨酸受体系统。最近的体外证据表明，N-甲基-D-天冬氨酸受体激活会显著改变视上核神经元的自发放电模式。在本研究中，我们评估体内的N-甲基-D-天冬氨酸受体是否有助于分泌血管加压素的神经元所呈现的特征性相位放电模式的形成。静脉注射盐酸氯胺酮（一种非竞争性N-甲基-D-天冬氨酸受体拮抗剂），以检查N-甲基-D-天冬氨酸受体阻断是否会影响视上核神经分泌神经元中观察到的有规律的自发放电。在戊巴比妥麻醉的Long-Evans大鼠中，从已识别的下丘脑视上核神经元进行细胞外记录。全身给予氯胺酮（≤1.5mg/kg）可有效抑制19个假定分泌血管加压素的细胞中的16个的自发放电相位。氯胺酮诱导的阻断呈剂量依赖性，完全可逆，并且与局部压力施加N-甲基-D-天冬氨酸所诱发的活动的完全阻断相关，但与α-氨基-3-羟基-5-甲基-异恶唑-4-丙酸受体激动剂所诱发的活动无关（6/6个细胞）。氯胺酮对逆行动作电位的阈值或形状没有可检测到的影响。相比之下，9/10个持续活动的神经元（假定分泌催产素）的活动不受相同剂量氯胺酮给药的影响。这些数据表明，N-甲基-D-天冬氨酸受体在调节大鼠视上核血管加压素神经元在体内呈现的自发放电相位活动模式的起始和维持中起重要作用。
