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5-羟色胺上行通路的5,7-二羟基色胺损伤的行为效应

Behavioral effects of 5, 7-dihydroxytryptamine lesions of ascending 5-hydroxytryptamine pathways.

作者信息

Hole K, Fuxe K, Jonsson G

出版信息

Brain Res. 1976 May 7;107(2):385-99. doi: 10.1016/0006-8993(76)90235-3.

DOI:10.1016/0006-8993(76)90235-3
PMID:944613
Abstract

In protriptyline (25 mg/kg) pretreated rats stereotactic 5,7-dihydroxytryptamine (5,7-DHT) lesions of the medial plus laternal 5-hydroxytryptamine (5-HE) bundles in the mesencephalon increased the 5-HT fluorescence in these bundles, and reduced the in vitro uptake of [3H] 5-HT in the hypothalamus to 16% of control values after 2 mug 5,7-DHT/4mul and 12% after 4 mug 5,7-DHT/4mul, and in the cortex cerebri to 35 and 34% of control values, respectively. Selective lesion of the medial 5-HT bundle reduced [3H] 5-HT uptake both in hypothalamus and in cortex cerebri to 45-48% of control values, while selective lesion of the lateral 5-HT bundles significantly reduced [3H] 5-HT uptake only in cortex (to 73-75%). No significant change was observed in [3H] noradreanaline uptake after any injection, or in [3H] 5-HT uptake after vehicle injections. Locomotor activity in an open field 3-10 days postoperatively was significantly reduced by lesions of the medial plus lateral 5-HT bundles. 5-Hdroxytryptophan (50 mg/kg) and a peripheral decarboxylase inhibitor (MK 486, 75 mg/kg) 17 days postoperatively induced a pronounced behavioral "5-HT syndrome" in these rats with medial plus lateral lesions but not in controls. Pain sensitivity, as measured by the hot plate test, was not changed by any lesion, even when tryptophan hydroxylase was partly inhibited with alpha-propyldopacetamide (100 mg/kg). Morphine analgesia and acquisition of a one-way avoidance response also were unchanged. Apomorphine (2 mg/kg)-induced locomotor activity and stereotyped behavior, as measured in an Animex activity meter, were not significantly different from control values in the 5,7-DHT groups. It was concluded that the medial 5-JT BUNDLE INNERVATES BOTH THE HYPOTHALAMUS AND THE CORTEX CEREBRI AND THE LATERAL 5-HT bundle mainly the cortex. These ascending 5-HT neurons are involved in maintaining open field ambulation. No wupport was obtained for the view that they are involved in pain mechanisms, in morphine-induced analgesia, in apomorphine-induced motor behavior, or in one-way avoidance learning.

摘要

在预先用普罗替林(25毫克/千克)处理的大鼠中,对中脑内侧加外侧5-羟色胺(5-HT)束进行立体定向5,7-二羟基色胺(5,7-DHT)损伤后,这些束中的5-HT荧光增加,并且在下丘脑中,2微克5,7-DHT/4微升注射后,[3H]5-HT的体外摄取降低至对照值的16%,4微克5,7-DHT/4微升注射后降低至12%;在大脑皮层中,分别降低至对照值的35%和34%。内侧5-HT束的选择性损伤使下丘脑和大脑皮层中[3H]5-HT的摄取均降低至对照值的45 - 48%,而外侧5-HT束的选择性损伤仅使大脑皮层中[3H]5-HT的摄取显著降低(至73 - 75%)。任何注射后,[3H]去甲肾上腺素摄取均未观察到显著变化,注射溶剂后[3H]5-HT摄取也未观察到显著变化。术后3 - 10天,内侧加外侧5-HT束损伤使旷场中的运动活动显著降低。术后17天,5-羟色氨酸(50毫克/千克)和外周脱羧酶抑制剂(MK 486,75毫克/千克)在这些内侧加外侧损伤的大鼠中诱发了明显的行为“5-HT综合征”,但在对照组中未诱发。通过热板试验测量的疼痛敏感性,即使在用α-丙基多巴酰胺(100毫克/千克)部分抑制色氨酸羟化酶时,也未因任何损伤而改变。吗啡镇痛和单向回避反应的习得也未改变。在Animex活动计中测量的阿扑吗啡(2毫克/千克)诱发的运动活动和刻板行为,在5,7-DHT组中与对照值无显著差异。得出的结论是,内侧5-HT束支配下丘脑和大脑皮层,外侧5-HT束主要支配大脑皮层。这些上行5-HT神经元参与维持旷场行走。未获得证据支持它们参与疼痛机制、吗啡诱导的镇痛、阿扑吗啡诱导的运动行为或单向回避学习的观点。

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