Wilson M A, Gallager D W
Eur J Pharmacol. 1987 Apr 29;136(3):333-43. doi: 10.1016/0014-2999(87)90306-2.
This study examined the effects of chronic diazepam treatment on GABA sensitivity of substantia nigra pars reticulata neurons and on the ability of benzodiazepines to enhance GABAergic responses of these neurons in rats. Chronic diazepam exposure failed to significantly alter the sensitivity of reticulata neurons to microiontophoretically applied GABA. However, following chronic diazepam treatment for 1 day, or 1, 3 or 7-11 weeks, reticulata neurons showed tolerance to additional systemically or iontophoretically applied benzodiazepines and displayed an increased firing rate following injection of Ro 15-1788. These changes were not apparent 24 h after cessation of chronic treatment. Thus, tolerance to the effects of benzodiazepines on reticulata neurons appeared to develop after a single day of diazepam exposure and to dissipate by 24 h after cessation of treatment. When compared to our previous studies on dorsal raphe neurons, these results demonstrate regional differences in neuronal responses to chronic diazepam exposure, which may help elucidate neural systems which are involved in tolerance to the various functional aspects of benzodiazepines.
本研究检测了慢性地西泮治疗对大鼠黑质网状部神经元γ-氨基丁酸（GABA）敏感性以及苯二氮䓬类药物增强这些神经元GABA能反应能力的影响。长期暴露于地西泮未能显著改变网状部神经元对微量离子导入GABA的敏感性。然而，在慢性地西泮治疗1天、1周、3周或7至11周后，网状部神经元对额外全身或离子导入应用的苯二氮䓬类药物产生耐受，且在注射Ro 15-1788后放电频率增加。在停止慢性治疗24小时后，这些变化并不明显。因此，对苯二氮䓬类药物作用于网状部神经元的耐受性似乎在暴露于地西泮1天后出现，并在停止治疗24小时后消失。与我们之前对中缝背核神经元的研究相比，这些结果表明神经元对慢性地西泮暴露的反应存在区域差异，这可能有助于阐明参与苯二氮䓬类药物各种功能方面耐受性的神经系统。
