OVARIAN ENDOCRINE STATUS MODULATES THE ANXIOLYTIC POTENCY OF DIAZEPAM AND THE EFFICACY OF GAMMA-AMINOBUTYRIC-ACID BENZODIAZEPINE RECEPTOR MEDIATED CHLORIDE-ION TRANSPORT
OVARIAN ENDOCRINE STATUS MODULATES THE ANXIOLYTIC POTENCY OF DIAZEPAM AND THE EFFICACY OF GAMMA-AMINOBUTYRIC-ACID BENZODIAZEPINE RECEPTOR MEDIATED CHLORIDE-ION TRANSPORT
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DOI：
10.1037/0735-7044.105.5.653
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发表时间：
1991-10-01
影响因子：
1.9
通讯作者：
KELLOGG, CK
中科院分区：
文献类型：
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作者：
BITRAN, D;HILVERS, RJ;KELLOGG, CK
研究了卵巢类固醇激素对γ-氨基丁酸（GABA）-苯二氮卓（BZD）受体氯离子通道复合物的行为和神经化学敏感性的影响。在不同卵巢状态的雌性大鼠中检查了高架十字迷宫中的运动活动和行为，以及动情前期和卵巢切除大鼠皮质突触神经体中GABA刺激的氯化物摄取的功效和效力。在哺乳期雌性动物中观察到，与间情期、动情前期、卵巢切除和妊娠雌性动物相比，对十字迷宫开放臂的探索显著增加。地西泮（DZ）的抗焦虑作用在卵巢切除雌性动物中降低，与发情前期雌性动物有关。尽管1.0 mg/kg DZ在发情前期雌性动物中具有显著的抗焦虑活性，但该剂量在卵巢切除雌性动物中无效，但通过注射苯甲酸雌二醇和孕酮可恢复。减少GABA刺激的氯离子转运在皮质突触神经小体从卵巢切除的女性，在从发情前期的女性，观察到的功效。此外，DZ对GABA刺激的氯离子内流的效力的促进作用，观察皮质突触神经小体从动情前期的女性是不存在的突触神经小体从卵巢切除的女性。这些结果进行了讨论，在卵巢类固醇和减少代谢产物对GABA-BZD受体介导的功能的影响。
The effect of ovarian steroid hormones on the behavioral and neurochemical sensitivity of the gamma-aminobutyric acid (GABA)-benzodiazepine (BZD) receptor chloride ion channel complex was studied. Locomotor activity and behavior in the elevated plus maze were examined in female rats of various ovarian states as was the efficacy and potency of GABA-stimulated chloride uptake in cortical synaptoneurosomes from proestrous and ovariectomized rats. A significant increase in the exploration of the open arms of the plus maze was observed in lactating females, in relation to diestrous, proestrous, ovariectomized, and pregnant females. The anxiolytic effect of diazepam (DZ) was decreased in ovariectomized females, in relation to proestrus females. Although 1.0 mg/kg DZ in proestrous females resulted in significant anxiolytic activity, this dose was ineffective in ovariectomized females but was reinstated by injection of estradiol benzoate and progesterone. A reduced efficacy of GABA-stimulated chloride ion transport in cortical synaptoneurosomes from ovariectomized females, in relation to that from proestrous females, was observed. Furthermore, the facilitative effect of DZ on the potency of GABA-stimulated chloride ion influx that was observed in cortical synaptoneurosomes from proestrous females was absent in synaptoneurosomes from ovariectomized females. These results are discussed in terms of the effect of ovarian steroids and reduced metabolites on GABA-BZD receptor-mediated functions.