EFFECTS OF ACUTE AND CHRONIC FENFLURAMINE ON SELF-STIMULATION AND ITS FACILITATION BY AMPHETAMINE
EFFECTS OF ACUTE AND CHRONIC FENFLURAMINE ON SELF-STIMULATION AND ITS FACILITATION BY AMPHETAMINE
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DOI：
10.1016/0014-2999(92)90432-4
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发表时间：
1992-06-17
影响因子：
5
通讯作者：
YUWILER, A
中科院分区：
文献类型：
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作者：
OLDS, ME;YUWILER, A
将释放血清素的 DL-芬氟拉明 (20 mg/kg) 和释放多巴胺的安非他明 (2 mg/kg) 给予经过杠铃推举训练的成年大鼠，以电刺激内侧前脑束。安非他明治疗可增强杠杆按压 1-2 小时。单次芬氟拉明治疗可迅速抑制自我刺激，并在 5-7 天内缓慢恢复至低于初始基础速率的速率。一周后的第二次治疗再次抑制了缓解率，并且缓解率回到了更低的基线。此时联合芬氟拉明-安非他明治疗可暂时取消杠杆按压 1-3 小时，随后增强反应 9-11 小时。血清素拮抗剂酮色林 (0.1 mg/kg) 可部分防止芬氟拉明的作用，但赛庚啶 (0.1 mg/kg i.p.) 则不然。在联合治疗中，血清素激动剂奎帕嗪 (0.5 mg/kg)，但不是二甲氧基碘苯基异丙胺 (DOI) (2.2 mg/kg)，部分替代了芬氟拉明。芬氟拉明显着降低额叶皮层、海马和尾壳核中的血清素和 5-羟基吲哚乙酸。中脑腹侧和中线区域受影响较小。芬氟拉明和安非他明联合治疗可升高额叶皮层、海马和尾壳核中的多巴胺水平，但不会升高中脑中的多巴胺水平。这些发现支持自我刺激行为中血清素-多巴胺的相互作用，并表明重复芬氟拉明治疗会导致慢性低水平血清素刺激和血清素储存能力降低。
DL-Fenfluramine (20 mg/kg) releasing serotonin and amphetamine (2 mg/kg) releasing dopamine were given to adult rats trained to bar press for electrical stimulation to the medial forebrain bundle. Amphetamine treatment enhanced lever-pressing for 1-2 h. A single fenfluramine treatment rapidly suppressed self-stimulation with slow recovery in 5-7 days to a rate below the initial basal rate. A second treatment a week later again suppressed response rate and rates returned to a still lower baseline. Combined fenfluramine-amphetamine treatment at this time transiently abolished lever pressing for 1-3 h followed by 9-11 h of enhanced responding. The serotonin antagonist, ketanserine (0.1 mg/kg), but not cyproheptadine (0.1 mg/kg i.p.), partially protected against the effects of fenfluramine. The serotonin agonist, quipazine (0.5 mg/kg), but not dimethoxyiodophenyliso-propylamine (DOI) (2.2 mg/kg), partially substituted for fenfluramine in the combined treatment. Fenfluramine markedly depleted serotonin and 5-hydroxyindoleacetic acid in frontal cortex, hippocampus, and caudate putamen. Ventral and midline midbrain regions were less affected. Combined fenfluramine and amphetamine treatment elevated dopamine levels in frontal cortex, hippocampus and caudate-putamen, but not in midbrain. These findings support a serotonin-dopamine interaction in self-stimulation behavior and suggest that repeated fenfluramine treatment results in chronic low level serotonergic stimulation and diminished serotonin storage capacity.