Enhanced anxiety observed in cocaine withdrawn rats is associated with altered reactivity of the dorsomedial prefrontal cortex.
Enhanced anxiety observed in cocaine withdrawn rats is associated with altered reactivity of the dorsomedial prefrontal cortex.
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DOI：
10.1371/journal.pone.0043535
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Bérod A
中科院分区：
文献类型：
--
作者：
El Hage C;Rappeneau V;Etievant A;Morel AL;Scarna H;Zimmer L;Bérod A
可卡因滥用者停止药物摄入通常会产生各种不良戒断症状，其中焦虑和抑郁相关行为在戒断初期普遍存在。本研究的目的是进一步了解可能导致这些病理状态的神经生物学失调。用可卡因或生理盐水治疗大鼠14天（20 mg/kg; i.p），并在停药后4周内以不同范式（升高+迷宫（EPM）、EPM张开臂限制和冲击探针埋入试验）评估焦虑相关行为。采用强迫游泳试验和蔗糖偏好试验评估抑郁样行为。总的来说，我们的研究结果表明，可卡因戒断引起了持续28天的持续高度焦虑，但对抑郁样行为没有影响。然后，我们使用Fos免疫组织化学来绘制EPM一只张开手臂的退出大鼠的神经元激活模式，并使用Fos免疫组织化学和谷氨酸脱羧酶或囊泡谷氨酸转运蛋白mrna的原位杂交双重标记程序来识别激活神经元的表型。我们的数据显示，可卡因戒断大鼠暴露于抬高的张开手臂时，焦虑加剧伴随着内侧前额叶皮层背侧（前扣带皮层和背前边缘皮层）、室旁丘脑核以及下丘脑外侧和前部区域的反应性改变。在内侧前额叶皮层，我们证实了在nacl处理的大鼠中，其背侧Fos表达与张开手臂诱导的冷冻呈负相关，而在可卡因戒断的大鼠中则没有。我们还发现超过65%的激活神经元是谷氨酸能投射神经元。目前的研究提供了新的见解，神经解剖区域和神经细胞类型，可能是在可卡因戒断期间病理性焦虑的基础。
Discontinuation of drug intake in cocaine abusers commonly produces a variety of adverse withdrawal symptoms among which anxiety and depression-related behavior are prevailing during the initial period of abstinence. The aim of this study was to provide further insight into the neurobiological dysregulations that might contribute to these pathological states. Rats were treated with cocaine or saline for 14 days (20 mg/kg; i.p) and anxiety-related behavior was assessed in different paradigms (elevated plus-maze (EPM), confinement to an open arm of the EPM and shock-probe burying tests) for up to 4 weeks after withdrawal. Depression-like behavior was assessed by the forced swim test and sucrose preference test. Altogether our results demonstrated that cocaine withdrawal induced persistent heightened levels of anxiety that last for at least 28 days but did not affect depression-like behavior. We then used Fos immunohistochemistry to map neuronal activation patterns in withdrawn rats confined to one open arm of an EPM, and a double labeling procedure using Fos immunohistochemistry and in situ hybridization of glutamic acid decarboxylase or vesicular glutamate transporter mRNAs to identify the phenotype of the activated neurons. Our data showed that the exacerbated anxiety observed in cocaine withdrawn rats exposed to an elevated open arm was accompanied by an altered reactivity of the dorsal part of the medial prefrontal cortex (anterior cingulate and dorsal prelimbic cortices), the paraventricular thalamic nucleus and the lateral and anterior areas of the hypothalamus. In the medial prefrontal cortex, we evidenced a negative correlation between Fos expression in its dorsal part and open arm-induced freezing in NaCl-treated rats but not in cocaine withdrawn rats. We also found that more than 65% of activated neurons were glutamatergic projection neurons. The present study provides new insights into the neuroanatomical regions and neuronal cell types that may underlie pathological anxiety during cocaine withdrawal.
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影响因子：
3.3
作者：
Albrechet-Souza, L.;Borelli, K. G.;Brandao, M. L.
通讯作者：
Brandao, M. L.
影响因子：
2.9
作者：
Filip, M;Faron-Górecka, A;Dziedzicka-Wasylewska, M
通讯作者：
Dziedzicka-Wasylewska, M
影响因子：
3.4
作者：
Basso, AM;Spina, M;Koob, GF
通讯作者：
Koob, GF
影响因子：
4.1
作者：
Contoreggi, C;Herning, RI;Hess, J
通讯作者：
Hess, J
影响因子：
10.6
作者：
Franklin, TR;Acton, PD;Childress, AR
通讯作者：
Childress, AR