Differential regional zif268 messenger RNA expression in an escalating dose/binge model of amphetamine-induced psychosis.
Differential regional zif268 messenger RNA expression in an escalating dose/binge model of amphetamine-induced psychosis.
复制标题
安非他明诱发精神病的剂量递增/暴饮暴食模型中差异区域 zif268 信使 RNA 表达。
DOI：
10.1016/s0306-4522(99)00510-2
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发表时间：
2000
期刊：
影响因子：
3.3
通讯作者：
Segal,DS
中科院分区：
文献类型：
--
作者：
Shilling,PD;Kelsoe,JR;Kuczenski,R;Segal,DS
安非他明引起的精神病通常与高剂量多次狂欢的兴奋剂滥用模式有关。为了在大鼠中模拟这些条件，我们使用了递增剂量/狂欢给药模式。动物预处理与递增剂量的安非他明（1.0- 8.0毫克/公斤）超过四天，然后暴露于9个每日狂饮（8.0毫克/公斤，每2小时;四次注射/天）。其他动物接受多次注射生理盐水、生理盐水后急性安非他明（8.0 mg/kg）或每日单次注射安非他明（8.0 mg/kg），同时进行递增剂量/狂欢治疗。最后一次注射后1小时，将所有动物断头，并使用zif 268反义探针原位杂交评估局部脑激活模式。急性安非他明导致ZIF 268信使RNA在背侧纹状体和背侧纹状体的显着升高。然而，而每日一次的安非他明治疗后，该指数不再高于控制水平的背侧纹状体，多次暴饮暴食的风险，需要的神经核恢复到基线。无颗粒岛叶皮质和内侧嗅结节zif 268信使RNA表达也显着增加急性安非他明治疗后，但不同的是，神经核和背侧纹状体，这种增加没有显着衰减，无论是单一的每日注射或多次狂欢治疗。Zif 268信使RNA在杏仁核外侧核的表达也保持高于基线后狂欢治疗。Zif 268信使RNA区域表达模式的这些变化与高剂量兴奋剂滥用者精神病发展的可能关系进行了讨论。
Amphetamine-induced psychosis is most often associated with a high-dose multiple binge pattern of stimulant abuse. To simulate these conditions in rats, we used an escalating dose/binge administration paradigm. Animals were pretreated with escalating doses of amphetamine (1.0–8.0mg/kg) over four days, then exposed to nine daily binges (8.0mg/kg every 2h; four injections/day). Other animals received either multiple injections of saline, saline followed by acute amphetamine (8.0mg/kg) or single daily injections of amphetamine (8.0mg/kg) in parallel with the escalating dose/binge treatment. One hour after the last injection, all animals were decapitated and regional brain activation patterns were assessed using in situ hybridization with antisense probes for zif268. Acute amphetamine resulted in a significant elevation of zif268 messenger RNA in both the nucleus accumbens and dorsal striatum. However, whereas after single daily amphetamine treatment this index was no longer elevated above control levels in the dorsal striatum, multiple binge exposures were required for the nucleus accumbens to return to baseline. Agranular insular cortex and medial olfactory tubercle zif268 messenger RNA expression was also markedly increased after acute amphetamine treatment but, unlike the nucleus accumbens and dorsal striatum, this increase was not significantly attenuated by either single daily injection or multiple binge treatment. Zif268 messenger RNA expression in the lateral nucleus of the amygdala also remained elevated above baseline after binge treatment. The possible relationships of these changes in zif268 messenger RNA regional expression patterns to the development of psychosis in high-dose stimulant abusers are discussed.