Degroot Aldemar, Wade Mark, Salhoff Craig, Davis Richard J, Tzavara Eleni T, Nomikos George G
Neuroscience Discovery Research, Eli Lilly and Company, Lilly Corporate Center-DC0510, Indianapolis, IN, 46285-0510, USA.
Eur J Pharmacol. 2004 Jun 16;493(1-3):103-9. doi: 10.1016/j.ejphar.2004.04.011.
There is evidence that the septohippocampal cholinergic system is activated in response to stressful stimuli. In addition, prior studies indicate that stimulating the hippocampal cholinergic neurotransmission increases open arm exploration in the elevated plus-maze. This raises the possibility that exposing the rat to an elevated platform, which would be similar to confining the animal to the open arms of the plus-maze, would alter hippocampal acetylcholine levels. Results from the present study suggest that an elevated platform can be used as an animal model of stress in that exposure to the platform significantly increased plasma corticosterone levels. Importantly, exposure to a platform significantly increased hippocampal acetylcholine efflux. Interestingly, the increase in plasma corticosterone and hippocampal acetylcholine levels upon exposure to an elevated platform could be prevented by chlordiazepoxide at a dose that had no effect on basal hippocampal acetylcholine or plasma corticosterone levels. However, the elevated platform-induced increase in hippocampal acetylcholine could not be blocked by prior administration of buspirone. These results provide direct evidence for the importance of the hippocampal cholinergic system in stress and provide validation for the elevated platform as a model of stress.
有证据表明,隔海马胆碱能系统会因应激刺激而被激活。此外,先前的研究表明,刺激海马胆碱能神经传递会增加高架十字迷宫中开放臂的探索行为。这就增加了一种可能性,即让大鼠暴露在高架平台上,这类似于将动物限制在十字迷宫的开放臂中,会改变海马中的乙酰胆碱水平。本研究结果表明,高架平台可作为一种应激动物模型,因为暴露于该平台会显著提高血浆皮质酮水平。重要的是,暴露于平台会显著增加海马乙酰胆碱外流。有趣的是,氯氮卓以对基础海马乙酰胆碱或血浆皮质酮水平无影响的剂量给药时,可预防暴露于高架平台后血浆皮质酮和海马乙酰胆碱水平的升高。然而,预先给予丁螺环酮并不能阻断高架平台诱导的海马乙酰胆碱增加。这些结果为海马胆碱能系统在应激中的重要性提供了直接证据,并验证了高架平台作为一种应激模型的有效性。