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将N-甲基-D-天冬氨酸受体拮抗剂注入大鼠背侧海马体后的抗抑郁样作用

Antidepressant-like effects of NMDA-receptor antagonist injected into the dorsal hippocampus of rats.

作者信息

Padovan C M, Guimarães F S

机构信息

Departamento de Farmacologia, Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo, Av. Bandeirantes 3900, 14049-900, SP, Ribeirão Prêto, Brazil.

出版信息

Pharmacol Biochem Behav. 2004 Jan;77(1):15-9. doi: 10.1016/j.pbb.2003.09.015.

DOI:10.1016/j.pbb.2003.09.015
PMID:14724037
Abstract

Exposure to uncontrollable stressors causes behavioral changes that have been related to depressive states in humans. Poststress intrahippocampal administration of amino-7-phosphonoheptanoic acid (AP-7), a glutamate NMDA-receptor antagonist, attenuated the restraint-induced decreased exploration of an elevated plus maze 24 h later. The objective of the study was to test if this treatment would also attenuate the increased immobility seem in the forced swim test (FST) due to preexposition to this stressful situation. Male Wistar rats with cannulae aimed at the dorsal hippocampus were submitted to 15 min of forced swimming and tested 24 h later. They received bilateral intrahippocampal injections of AP-7 (10 nmol) either before or after the pretest swimming session or before the test. Poststress treatment increased latency to display the first episode of immobility and tended to reduce total immobility time. The drug was ineffective when given before stress or before test and in nonstressed animals. This suggests that glutamate NMDA receptors located in the dorsal hippocampus are involved in the behavioral changes observed in the FST.

摘要

暴露于不可控应激源会导致行为改变,这种改变与人类的抑郁状态有关。应激后在海马体内注射谷氨酸N-甲基-D-天冬氨酸(NMDA)受体拮抗剂氨基-7-磷酸庚酸(AP-7),可在24小时后减轻束缚诱导的高架十字迷宫探索行为减少。本研究的目的是测试这种治疗方法是否也能减轻因预先暴露于这种应激情况而在强迫游泳试验(FST)中出现的不动时间增加。将带有插管并指向背侧海马体的雄性Wistar大鼠进行15分钟的强迫游泳,并在24小时后进行测试。它们在预测试游泳环节之前或之后或测试之前接受双侧海马体内注射AP-7(10纳摩尔)。应激后治疗增加了首次出现不动行为的潜伏期,并倾向于减少总不动时间。该药物在应激前或测试前给药时以及在非应激动物中无效。这表明位于背侧海马体的谷氨酸NMDA受体参与了FST中观察到的行为变化。

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