Drugan R C, Basile A S, Crawley J N, Paul S M, Skolnick P
Clinical Neuroscience Branch, NIMH, Bethesda, MD 20892.
Pharmacol Biochem Behav. 1988 Aug;30(4):1015-20. doi: 10.1016/0091-3057(88)90134-7.
Inescapable tailshock has been shown to elicit a tissue specific decrease in the density of peripheral benzodiazepine receptors (PBR). We have now explored possible mechanisms that may be responsible for this phenomenon. An 80 minute session of inescapable tailshock produced a reduction in the binding of [3H] Ro5-4864 to renal membranes at 0, 1 and 2 hr after stress, with values returning to control (naive) levels within 24 hr. In cardiac membranes, statistically significant reductions were observed only at 2 and 4 hr after stress. The role of the pituitary-adrenal axis and the sympathetic nervous system in this phenomenon was assessed by subjecting adrenalectomized, hypophysectomized, 6-OHDA-treated or control (sham-operated or saline-treated) rats to inescapable shock. Neither adrenalectomy, hypophysectomy, nor 6-OHDA pretreatment altered the stress-induced reduction in renal PBR. However, the stress-induced decrease in renal PBR was blocked by pretreatment with clonazepam (1 mg/kg), a potent anxiolytic with low affinity for PBR.
不可逃避的尾部电击已被证明会引起外周苯二氮䓬受体(PBR)密度的组织特异性降低。我们现在探讨了可能导致这种现象的机制。80分钟的不可逃避尾部电击在应激后0、1和2小时导致[3H]Ro5 - 4864与肾膜的结合减少,其值在24小时内恢复到对照(未处理)水平。在心肌膜中,仅在应激后2和4小时观察到统计学上显著的减少。通过对肾上腺切除、垂体切除、6 - 羟基多巴胺处理或对照(假手术或生理盐水处理)的大鼠施加不可逃避的电击,评估垂体 - 肾上腺轴和交感神经系统在这一现象中的作用。肾上腺切除、垂体切除或6 - 羟基多巴胺预处理均未改变应激诱导的肾PBR降低。然而,应激诱导的肾PBR降低被氯硝西泮(1毫克/千克)预处理所阻断,氯硝西泮是一种对PBR亲和力低的强效抗焦虑药。