腺苷A_1受体阻断剂对学习记忆的影响与胆碱能神经的关系

Effects of adenosine A_1 receptor antagonist on memory and its relationship with cholinergic nerve

目的:研究腺苷A1受体阻断剂对学习记忆的影响与中枢胆碱能神经的关系。方法:采用离体蟾蜍腹直肌生物测定法,通过离体器官测定仪,观察腺苷A1受体特异性阻断剂8-环戊-1,3-二丙基黄嘌呤(DPCPX)对小鼠脑内乙酰胆碱含量的影响;采用在体记录麻醉大鼠LTP的电生理学方法,观察DPCPX与东莨菪碱在海马齿状回基础突触传递活动和高频刺激诱导的LTP中作用的相关性。结果:DPCPX(0.3μg,icv)可显著增加小鼠脑内ACh含量,使蟾蜍腹直肌收缩幅度增强,该作用可被预先给予筒箭毒碱所拮抗;DPCPX(0.03μg)不影响大鼠海马齿状回突触传递活动,但可拮抗或取消东莨菪碱对高频刺激诱导LTP的抑制作用。结论:腺苷A1受体特异性阻断剂DPCPX可影响中枢胆碱能神经递质水平并改善东莨菪碱所致的记忆障碍。

Aim：To observe the effects of adenosine A1 blocking receptor on memory and its relationship with central cholinergic nerve. Methods： The influence of the selective adenosine A1 receptor antagonist 8-cyclopentyl-1, 3-dipropytxanthine（DPCPX）on acetylcholinechloride（ACh）concentration in the rat brain was studied through bioassay of the toad isolated musculus rectus abdominis using the isolated-organ measuring apparatus. Using electrophysiological technique to record the in situ long-term potentiation（LTP）, the relationship between DPCPX and scopolamine in both basic synaptic transmission and LTP induced by 200 Hz high-frequency stimulation （HFS）in the dentate gyrus of hippocampus of anesthetized rats was examined. Results： DPCPX （0.3μg, icv） could significantly increase the ACh concentration of the mouse brain and enhance the contraction amplitude of musculus rectus abdominis of the toad. But the effects of DPCPX could be antagonized by a pretreatment with tubocurarine. DPCPX（0.03μg, icv）did not exert the synaptic transmission of the dentate gyrus of hippocampus in rats, but could reverse the inhibitory effect of scopolamine on LTP induced by HFS. Conclusion： The selective adenosine A1 receptor antagonist, DPCPX, could influence the levels of central cholinergic neurotransmitter and improve the scopolamine-induced memory impairment.