Suzuki T, Ito T, Wellman S E, Ho I K
Department of Pharmacology and Toxicology, University of Mississippi Medical Center, Jackson, USA.
Eur J Pharmacol. 1998 Aug 7;354(2-3):145-51. doi: 10.1016/s0014-2999(98)00447-6.
We examined changes in benzodiazepine binding sites labeled by [3H]flunitrazepam in five nuclei of the thalamus, the central medial, central lateral, intermediodorsal, ventroposterior, and laterodorsal nuclei, in rats made tolerant to and dependent on pentobarbital. Animals were made tolerant by intracerebroventricular infusion with pentobarbital (300 microg (10 microl)(-1) h(-1) for six days) through pre-implanted cannulae. Pentobarbital dependence was assessed 24 h after abrupt withdrawal from pentobarbital. Pentobarbital-tolerant rats showed no significant change in [3H]flunitrazepam binding sites (Bmax and Kd) in any nucleus examined in the thalamus. In the rats made dependent on pentobarbital, significant increases in the Bmax of [3H]flunitrazepam binding without changes in Kd were noted in central medial and central lateral nuclei. GABAergic (gamma-aminobutyric acid) neurons in the ventrobasal nucleus and in nuclei in the midline group are important in seizure regulation and arousal. These findings suggest that alterations of benzodiazepine receptors in certain nuclei of thalami are involved in the physiological changes induced by pentobarbital dependence. There were no changes in the binding parameters for [3H]flunitrazepam in pentobarbital-tolerant rats.
我们研究了在对戊巴比妥产生耐受性和依赖性的大鼠中，[3H]氟硝西泮标记的苯二氮䓬结合位点在丘脑五个核团（中央内侧核、中央外侧核、中间背核、腹后核和背外侧核）中的变化。通过预先植入的套管向脑室内注入戊巴比妥（300微克（10微升）-1小时-1，持续6天）使动物产生耐受性。在突然停用戊巴比妥24小时后评估戊巴比妥依赖性。戊巴比妥耐受大鼠丘脑检查的任何核团中，[3H]氟硝西泮结合位点（Bmax和Kd）均无显著变化。在戊巴比妥依赖的大鼠中，中央内侧核和中央外侧核中[3H]氟硝西泮结合的Bmax显著增加，而Kd无变化。腹侧基底核和中线组核团中的γ-氨基丁酸（GABA）能神经元在癫痫发作调节和觉醒中起重要作用。这些发现表明，丘脑某些核团中苯二氮䓬受体的改变与戊巴比妥依赖性诱导的生理变化有关。戊巴比妥耐受大鼠中[3H]氟硝西泮的结合参数没有变化。
