Pelosi Gislaine G, Resstel Leonardo L B M, Soares Vanessa P, Zangrossi Hélio, Guimarães Francisco S, Corrêa Fernando M A
Department of Pharmacology, School of Medicine of Ribeirão Preto, University of São Paulo, Ribeirão Preto, São Paulo, Brazil.
Behav Pharmacol. 2009 May;20(3):252-9. doi: 10.1097/FBP.0b013e32832c7098.
The brain noradrenergic system has been implicated in the expression of defensive behaviors elicited by acute stress. The dorsal periaqueductal gray area (dPAG) is a key structure involved in the behavioral and cardiovascular responses elicited by fear and anxiety situations. Although there are noradrenergic terminals in the dPAG, few studies have investigated the role of noradrenaline (NA) in the dPAG on anxiety modulation. The aim of this study was to evaluate the effect of NA microinjection into the dPAG of rats subjected to two animal models of anxiety, the elevated plus-maze and the Vogel conflict test. Male Wistar rats implanted with a guide cannula aimed at the dPAG received microinjections of NA (3, 15, or 45 nmol/0.05 microl) or artificial cerebral spinal fluid into the dPAG immediately before being exposed to the elevated plus-maze or the Vogel conflict test. NA increased the exploration of the open arms and the number of enclosed arm entries in the elevated plus-maze. The increase in open arm exploration remained significant after being subjected to an analysis of covariance using the latter variable as covariate. Moreover, the NA microinjection into the dPAG did not increase general exploratory activity of animals subjected to the open-field test, indicating that the increase in open arm exploration cannot be attributed to a nonspecific increase in exploratory activity. In the Vogel test, the NA microinjection into the dPAG increased the number of punished licks without changing the number of nonpunished licks or interfering with the tail-flick test. The results, therefore, indicate that the NA microinjection into the dPAG produces anxiolytic-like effects, suggesting its possible involvement in the anxiety modulation.
大脑去甲肾上腺素能系统与急性应激引发的防御行为的表达有关。中脑导水管周围灰质背侧区（dPAG）是参与恐惧和焦虑情境引发的行为及心血管反应的关键结构。尽管dPAG中有去甲肾上腺素能终末，但很少有研究调查去甲肾上腺素（NA）在dPAG中对焦虑调节的作用。本研究的目的是评估向经历两种焦虑动物模型（高架十字迷宫和Vogel冲突试验）的大鼠dPAG中微量注射NA的效果。植入针对dPAG的引导套管的雄性Wistar大鼠，在暴露于高架十字迷宫或Vogel冲突试验之前，立即向dPAG中微量注射NA（3、15或45 nmol/0.05微升）或人工脑脊液。NA增加了高架十字迷宫中开放臂的探索次数和进入封闭臂的次数。以后者为协变量进行协方差分析后，开放臂探索次数的增加仍然显著。此外，向dPAG中微量注射NA并未增加进行旷场试验的动物的一般探索活动，这表明开放臂探索次数的增加不能归因于探索活动的非特异性增加。在Vogel试验中，向dPAG中微量注射NA增加了受罚舔舐的次数，而未改变未受罚舔舐的次数，也未干扰甩尾试验。因此，结果表明向dPAG中微量注射NA产生了抗焦虑样效应，提示其可能参与焦虑调节。
