Behavioral and biochemical effects of the antidepressant bupropion (Wellbutrin): evidence for selective blockade of dopamine uptake in vivo.
Behavioral and biochemical effects of the antidepressant bupropion (Wellbutrin): evidence for selective blockade of dopamine uptake in vivo.
复制标题
抗抑郁药安非他酮（Wellbutrin）的行为和生化作用：选择性阻断体内多巴胺摄取的证据。
DOI：
--
复制
发表时间：
1980
影响因子：
3.5
通讯作者：
R. Maxwell
中科院分区：
文献类型：
--
作者：
B. Cooper;T. Hester;R. Maxwell
安非他酮（BW 323U；安非他酮）是一种对人类具有抗抑郁作用的新型化合物，在对大鼠进行的“实验性无助”强迫游泳抗抑郁试验中，与丙咪嗪和阿米替林一样，安非他酮被发现可以减少不动。与阿波吗啡相比，高剂量的阿波吗啡会提高自动开放区域的运动活动，并产生刻板的嗅探。在内胆注射6-羟多巴胺前给予安非他酮或去甲基利米帕明，安非他酮对多巴胺神经元的破坏产生剂量相关的选择性拮抗作用，而在相同条件下，去甲基利米帕明对去甲肾上腺素能神经元的破坏产生剂量相关的选择性拮抗作用。安非他酮和6-羟多巴胺剂量变化的研究表明，当给予安非他酮50 mg/kg的剂量时，6-羟多巴胺对多巴胺消耗的选择性拮抗作用与剂量相关。100 mg/kg的安非他酮对去甲肾上腺素的消耗也有一定的拮抗作用。安非他酮也有选择性地逆转α -甲基-m-酪氨酸产生的多巴胺消耗，这与安非他酮是体内多巴胺摄取抑制剂的观点一致。多巴胺系统对安非他酮行为效应的重要性也进行了研究。当对6-羟多巴胺产生的多巴胺神经元慢性破坏的大鼠进行运动刺激作用测试时，安非他酮不能提高运动活性。用6-羟多巴胺治疗的大鼠产生相对选择性的去甲肾上腺素消耗，与对照组一样，对安非他酮有运动活动刺激反应。在“实验性无助”强迫游泳抗抑郁试验中，多巴胺或去甲肾上腺素消耗相似的大鼠也接受了低剂量安非他酮减少不动能力的测试。在本试验中，预先破坏多巴胺神经元可阻止安非他酮的活性。结果表明，安非他酮在体内是一种选择性多巴胺摄取抑制剂，多巴胺能系统在其中枢神经系统药理作用中起重要作用。
Bupropion (BW 323U; Wellbutrin), a novel compound with antidepressant effects in man, was found to reduce immobility in an "experimental helplessness" forced swimming antidepressant test in rats as did imipramine and amitriptyline. Higher doses produced elevated locomotor activity in an automated open field and produced stereotyped sniffing which was contrasted with apomorphine. When bupropion or desmethylimipramine was given before intracisternal injections of 6-hydroxydopamine, bupropion produced a dose-related selective antagonism of the destruction of dopamine neurons, while under the same conditions, desmethylimipramine produced a dose-related selective antagonism of the destruction of noradrenergic neurons. Studies in which the dose of bupropion and the dose of 6-hydroxydopamine were varied revealed that a dose-related selective antagonism of dopamine depletion by 6-hydroxydopamine occurred when doses up to and including 50 mg/kg i.p. to bupropion were administered. Some antagonism of norepinephrine depletion also occurred at 100 mg/kg of bupropion i.p. Bupropion also selectively reversed the dopamine depletion produced by alpha-methyl-m-tyrosine, a finding which is consistent with the view that bupropion is a dopamine uptake inhibitor in vivo. The importance of dopamine systems for the behavioral effects of bupropion were also studied. When the locomotor stimulant effects of bupropion were tested in rats with chronic destruction of dopamine neurons produced by 6-hydroxydopamine, bupropion failed to elevate locomotor activity. Rats treated with procedures using 6-hydroxydopamine to produce relatively selective norepinephrine depletions responded to bupropion with locomotor activity stimulation like controls. Rats with similar depletions of either dopamine or norepinephrine were also tested for the ability of low doses of bupropion to reduce immobility in the "experimental helplessness" forced swim antidepressant test. Prior destruction of dopamine neurons prevented activity of bupropion in this test. Results indicate that bupropion is a selective dopamine uptake inhibitor in vivo and that dopaminergic systems play an important role in its central nervous system pharmacology.