Park C H, Hitri A, Lukacs L G, Deutsch S I
Psychiatry Service, Department of Veterans Affairs, Medical Center, Washington, DC 20422.
Pharmacol Biochem Behav. 1993 Jun;45(2):299-304. doi: 10.1016/0091-3057(93)90242-l.
The ability of flurazepam to antagonize the electrical precipitation of tonic hindlimb extension is reduced 24 h after mice are forced to swim for 10 min in cold water (6 degrees C). Presumably, this reduction in flurazepam's antiseizure efficacy reflects an environmental stress-induced modification of the GABAA receptor complex. The current study employed a variety of complementary in vitro approaches to characterize the delayed effects of cold-water swim stress on binding parameters of the GABAA receptor complex that may be associated with flurazepam's reduced antiseizure efficacy. The specific binding of [3H]flunitrazepam and the potentiation of this binding by chloride ions did not change after stress in the cerebral cortex, hippocampus, and cerebellum. Moreover, swim stress did not alter the ability of GABA to inhibit the binding of [35S]t-butylbicyclophosphorothionate (TBPS), a ligand that is a specific biochemical marker of the GABA-associated chloride ionophore, to crude membranes prepared from the cerebral cortex and cerebellum. Swim stress was associated with alterations of the specific binding of [3H]Ro 15-1788, a benzodiazepine receptor antagonist, to crude hippocampal and cerebellar membranes. The results are considered in the context of new insights derived from molecular cloning studies of the GABAA receptor complex.
在小鼠被迫于冷水（6摄氏度）中游泳10分钟后24小时，氟西泮拮抗强直性后肢伸展电惊厥的能力降低。据推测，氟西泮抗癫痫疗效的这种降低反映了环境应激诱导的GABAA受体复合物的改变。当前研究采用了多种互补的体外方法来表征冷水游泳应激对GABAA受体复合物结合参数的延迟影响，这些影响可能与氟西泮降低的抗癫痫疗效相关。应激后，大脑皮质、海马体和小脑中，[3H]氟硝西泮的特异性结合以及氯离子对这种结合的增强作用均未改变。此外，游泳应激并未改变GABA抑制[35S]叔丁基双环磷硫代酸盐（TBPS）结合的能力，TBPS是一种与GABA相关的氯离子通道特异性生化标记物，可与从大脑皮质和小脑制备的粗膜结合。游泳应激与苯二氮䓬受体拮抗剂[3H]Ro 15 - 1788与海马体和小脑粗膜的特异性结合改变有关。我们结合从GABAA受体复合物分子克隆研究中获得的新见解来考虑这些结果。
