Shah Akeel A, Treit Dallas
Department of Psychology, University of Alberta, P217 Biological Sciences Building, T6G 2E9, Edmonton, AB, Canada.
Brain Res. 2004 Jan 16;996(1):31-40. doi: 10.1016/j.brainres.2003.10.015.
Previous research has shown that lesions of the medial prefrontal cortex (MPFC) inhibit fear-related behavior in rats (Brain Res. 969 (2003) 183-194). However, at present little is known about the role of specific neurotransmitter receptor systems within the MPFC in the mediation of fear and anxiety. For example, extensive research has demonstrated the effectiveness of benzodiazepines in decreasing fear-related behavior. However, no research has yet been published regarding the effects of micro-infusions of benzodiazepines, or any other GABA-A receptor agonist, into the MPFC. In addition, previous work has suggested that there may be functional differences between the dorsal and ventral subregions of the MPFC in regard to fear and anxiety. Therefore, the present study examined the effects of dorsal and ventral MPFC infusions of the benzodiazepine midazolam in two well-validated animal models of anxiety, the elevated plus maze and the shock probe burying test. The results showed that bilateral (5 microg/side) infusions of midazolam into the MPFC produced anxiolytic effects in both behavioural tests, without affecting general activity or pain sensitivity. Furthermore, these anxiolytic effects were found in both the dorsal and ventral regions of the MPFC. The present findings indicate that the benzodiazepine receptors of the MPFC are capable of modulating fear-related behaviors.
先前的研究表明,内侧前额叶皮质(MPFC)损伤会抑制大鼠的恐惧相关行为(《脑研究》969(2003)183 - 194)。然而,目前对于MPFC内特定神经递质受体系统在恐惧和焦虑调节中的作用知之甚少。例如,大量研究已证明苯二氮䓬类药物在减少恐惧相关行为方面的有效性。然而,关于向MPFC微量注射苯二氮䓬类药物或任何其他GABA - A受体激动剂的效果,尚未有研究发表。此外,先前的研究表明,MPFC的背侧和腹侧子区域在恐惧和焦虑方面可能存在功能差异。因此,本研究在两种经过充分验证的焦虑动物模型,即高架十字迷宫和电击探针埋埋试验中,研究了向MPFC背侧和腹侧注射苯二氮䓬类药物咪达唑仑的效果。结果表明,向MPFC双侧(每侧5微克)注射咪达唑仑在两种行为测试中均产生抗焦虑作用,且不影响一般活动或疼痛敏感性。此外,在MPFC的背侧和腹侧区域均发现了这些抗焦虑作用。本研究结果表明,MPFC的苯二氮䓬受体能够调节恐惧相关行为。