Sensitivity to ethanol across development in rats:: Comparison to [3H]zolpidem binding
Sensitivity to ethanol across development in rats:: Comparison to [3H]zolpidem binding
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DOI：
10.1097/00000374-199810000-00018
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发表时间：
1998-10-01
影响因子：
3.2
通讯作者：
Breese, GR
中科院分区：
文献类型：
--
作者：
Moy, SS;Duncan, GE;Breese, GR
先前的研究表明，在28至30日龄时进行测试的大鼠对乙醇的镇静作用表现出明显的不敏感性。在本研究中，不同年龄的大鼠进行了空中翻正急性乙醇（3 g/kg）治疗。将这些结果与非典型苯二氮卓唑吡坦（3和5 mg/kg）和戊巴比妥（10和15 mg/kg）的作用进行比较。与断奶前大鼠（20日龄）或老龄大鼠（65 - 75日龄）相比，25、28或35日龄试验动物受到乙醇的损害显著较少，而25或28日龄试验动物受到较高剂量唑吡坦的损害较少。使用戊巴比妥时，最明显的年龄相关趋势是20日龄大鼠的损伤更大。由于乙醇可能在[H-3]唑吡坦选择性标记的相同I型GABA（A）受体位点上具有活性，因此测定了不同年龄大鼠的[H-3]唑吡坦结合水平。尽管一些脑区显示在发育过程中[H-3]唑吡坦的结合逐渐增加，但其他脑区显示从第12或17天至第20天结合增加，然后在第20、25和28天结合水平达到平台，到第36或60天进一步增加。在扣带皮层、内侧隔核、苍白球、下丘、红核和小脑中观察到这种模式。总体而言，结果表明，对乙醇镇静作用的次敏感期与[H-3]唑吡坦靶向的GABA（A）受体位点发育模式的变化一致。
Previous research has suggested that rats tested at 28 to 30 days of age show a marked subsensitivity to the sedative effects of ethanol. In the present study, rats of different ages were tested for aerial righting following acute ethanol (3 g/kg) treatment. These results were compared with the effects of the atypical benzodiazepine zolpidem (3 and 5 mg/kg) and pentobarbital (10 and 15 mg/kg). Animals tested at 25, 28, or 35 days of age were significantly less impaired by ethanol than preweanling rats (age 20 days) or older rats (age 65 to 75 days), whereas animals tested at 25 or 28 days of age were less impaired by the higher dose of zolpidem. With pentobarbital, the most distinct age-related trend was greater impairment in 20-day-old rats. Because ethanol may be active at the same type I GABA(A) receptor site selectively labeled by [H-3]zolpidem, levels of [H-3]zolpidem binding were determined for rats of different ages. Although some brain regions showed progressive increases in binding of [H-3]zolpidem across development, other regions demonstrated increased binding from day 12 or 17 to day 20, then a plateau of binding levels across days 20, 25, and 28, with further increases occurring by day 36 or day 60. This pattern was observed in the cingulate cortex, medial septal nucleus, globus pallidus, inferior colliculus, red nucleus, and cerebellum. Overall, the results indicate that the period of subsensitivity to the sedative effects of ethanol is coincident with a change in the developmental pattern of GABA(A) receptor sites targeted by [H-3]zolpidem.