Herpes virus-mediated preproenkephalin gene transfer in the ventral striatum mimics behavioral changes produced by olfactory bulbectomy in rats.
Herpes virus-mediated preproenkephalin gene transfer in the ventral striatum mimics behavioral changes produced by olfactory bulbectomy in rats.
复制标题
疱疹病毒介导的腹侧纹状体中的前脑啡肽原基因转移模拟了大鼠嗅球切除术产生的行为变化。
DOI:
10.1016/s0006-8993(03)03337-7
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发表时间:
2003
期刊:
影响因子:
2.9
通讯作者:
Holmes,PhilipV
中科院分区:
文献类型:
--
作者:
Primeaux,StefanyD;Wilson,MarleneA;Wilson,StevenP;Guth,AmandaN;Lelutiu,NadiaB;Holmes,PhilipV
The syndrome of behavioral, physiological, and neurochemical changes caused by ablation of the olfactory bulbs (OBX) in rats serves as a reliable and well-validated model of depression. Previous experiments have demonstrated that OBX leads to increased expression of the preproenkephalin (ENK) gene in the olfactory tubercle (OT) portion of the ventral striatum in rats. The aim of the present experiments was to investigate the role of OBX-induced ENK overexpression in the OT in the behavioral abnormalities exhibited by bulbectomized rats. A recombinant herpes virus carrying human preproENK cDNA was used to manipulate ENK gene expression in the OT of bulbectomized and sham-operated rats. Motivational deficits were assessed by the sucrose preference test, and ‘agitation-like’ behaviors were measured with the novel open field and footshock-induced freezing tests. ENK gene transfer in sham-operated rats mimicked some of the effects of OBX; it decreased freezing behavior in response to mild footshock and produced behavioral activation in the open field. In another experiment, virally mediated ENK gene transfer into the OT of intact rats decreased footshock-induced freezing, and this effect was reversed by naltrexone administration. PreproENK gene transfer into the OT did not produce analgesic effects in the tail-flick test. No effects on freezing behavior were observed following preproENK gene transfer into the frontal cortex. An additional experiment revealed that naltrexone administration attenuated the OBX-induced abnormality in freezing behavior. The results indicate that overexpression of the preproENK gene in the ventral striatum may mediate the ‘agitation-like’ behavior exhibited by bulbectomized rats.