Long-term effects on cortical glutamate release induced by prenatal exposure to the cannabinoid receptor agonist (R)-(+)-[2,3-dihydro-5-methyl-3-(4-morpholinyl-methyl)pyrrolo[1,2,3-de]-1,4-benzoxazin-6-yl]-1-naphthalenylmethanone:: An in vivo microdialysis study in the awake rat
Long-term effects on cortical glutamate release induced by prenatal exposure to the cannabinoid receptor agonist (R)-(+)-[2,3-dihydro-5-methyl-3-(4-morpholinyl-methyl)pyrrolo[1,2,3-de]-1,4-benzoxazin-6-yl]-1-naphthalenylmethanone:: An in vivo microdialysis study in the awake rat
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DOI：
10.1016/j.neuroscience.2003.10.034
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发表时间：
2004-01-01
期刊：
影响因子：
3.3
通讯作者：
Ferraro, L
中科院分区：
文献类型：
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作者：
Antonelli, T;Tanganelli, S;Ferraro, L
本体内微透析研究的目的是探讨在孕期以0.5毫克/千克的剂量（从妊娠第5天到第20天皮下注射）暴露于大麻素1型（CB1）受体激动剂甲磺酸WIN55,212 - 2（WIN；(R)-(+)-[2,3 - 二氢 - 5 - 甲基 - 3 - (4 - 吗啉基 - 甲基)吡咯并[1,2,3 - de]-1,4 - 苯并恶嗪 - 6 - 基]-1 - 萘基甲酮），此剂量既不引起畸形也无明显毒性迹象，是否会影响成年（90日龄）大鼠皮质细胞外谷氨酸水平。孕期用WIN处理对母鼠体重增加、孕期长度和出生时的窝仔数均无显著影响。在妊娠期间暴露于WIN的成年大鼠大脑皮质中，基础和钾离子诱发的透析液谷氨酸水平低于溶媒处理的母鼠所产的大鼠。在两组动物中，WIN（0.1毫克/千克，腹腔注射）均增加了透析液谷氨酸水平。然而，虽然用选择性受体拮抗剂SR141716A阻断CB1受体完全抵消了妊娠期间暴露于溶媒的大鼠中WIN诱导的增加，但未能拮抗WIN处理的母鼠所产大鼠的这种增加。这些发现表明，在孕期以不与严重畸形和/或明显毒性迹象相关的浓度暴露于CB1受体激动剂WIN，会诱导皮质谷氨酸能功能的永久性改变。文中讨论了这些影响可能至少在一定程度上是大麻使用者后代某些认知缺陷的基础的可能性。（C）2004年国际脑研究组织。由爱思唯尔有限公司出版。保留所有权利。
The aim of the present in vivo microdialysis study was to investigate whether prenatal exposure to the CB1 receptor agonist WIN55,212-2 mesylate (WIN; (R)-(+)-[2,3-dihydro-5-methyl-3-(4-morpholinyl-methyl)pyrrolo[1,2,3-de]- 1,4-benzoxazin-6-yl]-1-naphthalenylmethanone), at a dose of 0.5 mg/kg (s.c. from the fifth to the 20th day of gestation), that causes neither malformations nor overt signs of toxicity, influences cortical glutamate extracellular levels in adult (90-day old) rats.Dam weight gain, pregnancy length and litter size at birth were not significantly affected by prenatal treatment,with WIN. Basal and K+-evoked dialysate glutamate levels were lower in the cerebral cortex of adult rats exposed to WIN during gestation than in those born from vehicle-treated mothers. In both group of animals WIN (0.1 mg/kg, i.p.) increased dialysate glutamate levels. However, while the blockade of the CB1 receptors with the selective receptor antagonist SR141716A completely counteracted the WIN-induced increase in those rats exposed to vehicle during gestation, it failed to antagonise the increase in those born from WIN-treated dams.These findings suggest that prenatal exposure to the CB1 receptor agonist WIN, at a concentration which is not associated with gross malformations and/or overt signs of toxicity, induces permanent alterations in cortical glutamatergic function. The possibility that these effects might underlie, at least in part, some of the cognitive deficits affecting the offspring of marijuana users is discussed. (C) 2004 IBRO. Published by Elsevier Ltd. All rights reserved.