The effect of (+)‐amphetamine on various central and peripheral catecholamine‐containing neurones
The effect of (+)‐amphetamine on various central and peripheral catecholamine‐containing neurones
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(+)-苯丙胺对各种中枢和外周含儿茶酚胺神经元的影响
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发表时间：
1966
期刊：
影响因子：
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通讯作者：
B. Hamberger
中科院分区：
文献类型：
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作者：
A. Carlsson;M. Lindqvist;K. Fuxe;B. Hamberger
（+）-安非他明对各种含儿茶酚胺的中枢和外周神经元的作用在以前的大鼠脑实验中（Carlsson，Lindqvist，Dahlstrom，Fuxe和Masuoka，1965），安非他明类物质能够引起颗粒外儿茶酚胺的释放，即位于储存颗粒外的神经元内的儿茶酚胺的释放。此外，发现在大剂量下，这些药物还可引起颗粒释放儿茶酚胺。在目前的工作中，（+）-安非他明的效果已被进一步检查其对颗粒外胺的影响。特别注意不同的儿茶酚胺神经元系统对这种药物的敏感性。使用200-300 g成年雄性Sprague-Dawley大鼠。由于颗粒外胺部分通常看起来很小，所以实验是在胺储存被利血平排空的动物身上进行的。然后通过单胺氧化酶抑制剂尼阿拉胺，然后通过儿茶酚胺前体~-3，4-二羟基苯丙氨酸（L-多巴）来加载颗粒外空间。体内实验。动物用利血平10 mg/kg，i. p.，在处死前20-22小时，腹腔注射尼阿酰胺100 mg/kg，死前4小时，和多巴，25-50 mg/kg，皮下注射，死亡前30分钟（+）-安非他明以不同剂量（以碱计）在多巴前15 min给药。多巴胺、去甲肾上腺素和3-甲氧基酪胺采用荧光法测定（Bertler，Carlsson & Rosengren，1958 ; Carlsson &沃尔德克，1958 ; Carlsson & Lindqvist，1962; Carlsson & Lindqvist，1963; Carlsson &沃尔德克，1964）。取15只动物用于脑、心脏和输精管中单胺的细胞定位（法尔克，Hillarp，Thieme & Torp，1962;法尔克，1962;参见Hillarp，Fuxe & Dahlstrom，1965的综述），一个对照组（4只动物）和两个接受（+）-安非他明的组（0.75 mg/kg，5只动物和0.4 mg/kg，6只动物）。体外实验。将利血平处理的大鼠（10 mg/kg，处死前12-18小时）的新纹状体、下丘脑、新皮质和输精管的脑切片与1或0.03 μ g/ml的cr-甲基去甲肾上腺素孵育30 min（Hamberger & Masuoka，1965）。在测试实验中，将切片与（+）-安非他明（0.0075-0.75 pg/ml）预孵育15 min，然后将cr-甲基去甲肾上腺素加入培养基中。
The effect of ( +)-amphetamine on various central and peripheral catecholaminecontaining neurones SiR,-In previous experiments with rat brain (Carlsson, Lindqvist, Dahlstrom, Fuxe & Masuoka, 1965), support was obtained for the view that substances of the amphetamine group are capable of causing the release of extragranular catecholamines, that is, of catecholamines located intraneuronally outside the storage granules. Furthermore, it was found that in large doses these drugs may also cause the release of catecholamines from the granules. In the present work the effect of (+)-amphetamine has been further examined for its effect on extragranular amines. Special attention has been paid to the sensitivity of different catecholamine neurone systems to this drug. Adult, male Sprague-Dawley rats, 200-300 g, were used. Since the extragranular amine fraction normally seems to be very small, the experiments were made on animals whose amine stores had been emptied by reserpine. Loading of the extragranular space was then brought about by means of the monoamine oxidase inhibitor nialamide, followed by the catecholamine precursor ~-3,4-dihydroxyphenylalanine (L-dopa). In vivo experiments. The animals were treated with reserpine, 10 mg/kg, i.p., 20-22 hr before being killed, nialamide, 100 mg/kg, i.p., 4 hr before death, and dopa, 25-50 mg/kg, s.c., 30 min before death. (+)-Amphetamine was administered in various doses (calculated as the base) 15 min before the dopa. Dopamine, noradrenaline and 3-methoxytyramine were measured fluorimetrically (Bertler, Carlsson & Rosengren, 1958 ; Carlsson & Waldeck, 1958 ; Carlsson & Lindqvist, 1962; Carlsson & Lindqvist, 1963; Carlsson & Waldeck, 1964). Fifteen animals were taken for the cellular localization of monoamines in the brain, heart and vas deferens (Falck, Hillarp, Thieme & Torp, 1962; Falck, 1962; see review by Hillarp, Fuxe & Dahlstrom, 1965), one control group (4 animals) and two groups receiving (+)-amphetamine (0.75 mg/kg, 5 animals, and 0.4 mg/kg, 6 animals). In vitro experiments. Brain slices of the neostriatum, hypothalamus, neocortex and the vas deferens of reserpine-treated rats (10 mg/kg, 12-18 hr before killing) were incubated for 30 rnin (Hamberger & Masuoka, 1965) with cr-methylnoradrenaline, 1 or 0.03 pg/ml. In the test experiments the slices were preincubated for 15 min with (+)-amphetamine (0.0075-0.75 pg/ml), whereupon the cr-methylnoradrenaline was added to the medium.