IMMUNOCYTOCHEMICAL EVIDENCE FOR METHAMPHETAMINE-INDUCED SEROTONERGIC AXON LOSS IN THE RAT-BRAIN
IMMUNOCYTOCHEMICAL EVIDENCE FOR METHAMPHETAMINE-INDUCED SEROTONERGIC AXON LOSS IN THE RAT-BRAIN
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DOI：
10.1002/syn.890090405
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发表时间：
1991-12-01
期刊：
影响因子：
2.3
通讯作者：
MOLLIVER, ME
中科院分区：
文献类型：
--
作者：
AXT, KJ;MOLLIVER, ME
用免疫细胞化学方法显示中枢5-羟色胺(5-HT)轴突，以评估大鼠注射甲基苯丙胺后神经密度的急性和长期变化。D-甲基苯丙胺(d-MA)对两种形态不同的5-羟色胺(5-羟色胺)轴突(细小和珠状)有不同的影响，给药后4h和2周，细5-羟色胺能轴突密度选择性降低。100 mg/kg或15 mg/kg剂量的d-MA处理4小时后，大鼠脑内细小轴突的5-羟色胺含量显著减少，而珠状轴突的5-羟色胺含量未见减少。在接受d-MA治疗1周或2周的大鼠中，有30%的大鼠观察到5-羟色胺轴突的持续性丢失，这会导致5-羟色胺生化标记物的长期缺陷。在出现去神经支配的那部分动物中，d-MA选择性地消融细小的5-羟色胺能纤维，而保留珠状5-羟色胺能纤维。因此，d-MA类似于其他苯丙胺衍生物(如对氯苯丙胺、3，4-亚甲基二氧基苯丙胺)，因为它选择性地作用于形态上不同的一类5-羟色胺轴突，但不同之处在于，它只在一小部分动物中产生长期的轴突丢失。这些数据提供了甲基苯丙胺给药后5-羟色胺轴突丢失的形态学证据，并进一步证实了特定形态亚型的5-羟色胺能轴突对替代苯丙胺的神经毒性效应的不同易感性。
Central serotonin (5-HT) axons were visualized by immunocytochemistry to assess both acute and long-lasting changes in innervation density following methamphetamine administration to rats. Two morphologically distinct subtypes of 5-HT axons (fine and beaded) were differentially affected by d-methamphetamine (d-MA); the density of fine serotonergic axons was selectively decreased both 4 hours and 2 weeks after administration of d-MA. Acute depletion of 5-HT from fine axons, but not from beaded axons, was observed in the brains of all rats treated 4 hours previously with either a 100 mg/kg or 15 mg/kg dose of d-MA. Persistent loss of 5-HT axons was observed in 30% of rats treated 1 or 2 weeks previously with doses of d-MA which produce long-term deficits in biochemical markers for 5-HT. In the fraction of animals that exhibited denervation, fine serotonergic fibers were selectively ablated by d-MA, but beaded serotonergic fibers were spared. Thus, d-MA is similar to other amphetamine derivatives (e.g., p-chloroamphetamine, 3,4-methylenedioxyamphetamine) in that it acts selectively upon a morphologically distinct class of 5-HT axons but differs in that it produces long-lasting axon loss in only a fraction of animals.These data provide morphologic evidence of 5-HT axon loss following methamphetamine administration and further confirm the differential vulnerability of a particular morphological subtype of serotonergic axons to the neurotoxic effects of substituted amphetamines.