Lim L W, Temel Y, Sesia T, Vlamings R, Visser-Vandewalle V, Steinbusch H W M, Blokland A
Department of Neuroscience, Maastricht University, Maastricht, The Netherlands.
Neuroscience. 2008 Jul 31;155(1):164-73. doi: 10.1016/j.neuroscience.2008.05.038. Epub 2008 Jun 5.
5-HT(1A) modulation within the midbrain periaqueductal gray (PAG) is closely associated with anxiety- or panic-like behavior. Several findings have demonstrated that the properties of buspirone (a 5-HT(1A) partial agonist) would function as either anxiolytic or panicolytic in both clinical and laboratory animal research. In this study, we have investigated the neuronal activity occurring within the different regions of the PAG induced by buspirone treatment. Twenty-eight albino Wistar rats (350-400 g) were injected with either acute or chronic saline/buspirone (each, n=7), respectively. Our results show that buspirone treatment reduced locomotor activity, body weight and fecal boli, particularly in the chronic buspirone group. Two-way ANOVA revealed a significant decrease of c-Fos-immunoreactive (ir) cells expression in all regions of the rostral PAG after both acute and chronic buspirone (acute buspirone (AB) and chronic buspirone (CB), respectively) treatment. However, no effects on c-Fos-ir were detected in the caudal lateral periaqueductal gray (lPAG) and ventrolateral periaqueductal gray (vlPAG) in both the AB and CB groups, and in the dorsolateral periaqueductal gray (dlPAG) of the CB group. Interestingly, c-Fos-ir cells in the dorsomedial periaqueductal gray (dmPAG) column were reduced consistently in both the rostral and caudal PAG in both AB and CB groups. Besides, in all regions the number of c-Fos-ir cells was higher in the AB than in the CB group with exception of the rostral lPAG. In conclusion, the main anxiolytic effect of buspirone was specifically localized in all regions of the rostral PAG and in the caudal dmPAG. However, the caudal dlPAG, lPAG and vlPAG were found to be ineffective to buspirone treatment, probably due to their distinctive function in mediating higher level of anxiety in defensive behavior. This indicates that the longitudinal anatomical structure of the PAG possesses a different level of receptor sensitivity of 5-HT(1A) in the pathophysiology of anxiety and panic disorder.
中脑导水管周围灰质（PAG）内的5-羟色胺（5-HT）（1A）调节与焦虑样或惊恐样行为密切相关。多项研究结果表明，在临床和实验动物研究中，丁螺环酮（一种5-HT（1A）部分激动剂）的特性可起到抗焦虑或抗惊恐作用。在本研究中，我们调查了丁螺环酮处理诱导的PAG不同区域内发生的神经元活动。28只白化Wistar大鼠（350 - 400克）分别注射急性或慢性生理盐水/丁螺环酮（每组n = 7）。我们的结果表明，丁螺环酮处理降低了运动活性、体重和粪便团块，尤其是在慢性丁螺环酮组中。双向方差分析显示，急性和慢性丁螺环酮（分别为急性丁螺环酮（AB）和慢性丁螺环酮（CB））处理后，吻侧PAG所有区域中c-Fos免疫反应性（ir）细胞表达均显著降低。然而，在AB组和CB组的尾侧外侧导水管周围灰质（lPAG）和腹外侧导水管周围灰质（vlPAG）以及CB组的背外侧导水管周围灰质（dlPAG）中，未检测到对c-Fos-ir的影响。有趣的是，在AB组和CB组中，吻侧和尾侧PAG的背内侧导水管周围灰质（dmPAG）柱中的c-Fos-ir细胞均持续减少。此外，除吻侧lPAG外，在所有区域中，AB组的c-Fos-ir细胞数量均高于CB组。总之，丁螺环酮的主要抗焦虑作用特异性地定位于吻侧PAG的所有区域和尾侧dmPAG。然而，发现尾侧dlPAG、lPAG和vlPAG对丁螺环酮处理无效，这可能是由于它们在介导防御行为中较高水平焦虑方面具有独特功能。这表明PAG的纵向解剖结构在焦虑和惊恐障碍的病理生理学中具有不同水平的5-HT（1A）受体敏感性。
