5-HT_(1A)和5-HT_2受体功能与觉醒、睡眠成分关系的研究

目的　观察 5 HT1A受体激动剂 8 OH DPAT和HT2受体拮抗剂利坦色林 (ritanserin)对大鼠清醒和睡眠成分的影响 ,给予 5 HT1A受体激动剂和剥夺REM睡眠后皮层 5 HT2 受体结合能力的变化 ,进一步分析两种 5 HT受体亚型之间的关系以及 5 HT2 受体在睡眠中的作用。方法　利用大鼠睡眠自动分析系统定量分析清醒和睡眠成分的变化 ,注射PCPA制作剥夺睡眠的大鼠模型 ,水上平台法制作剥夺REM睡眠的大鼠模型 ,利用放射配体结合实验研究配体与受体结合力的变化。结果　 8 OH DPAT小剂量 (0 0 1mg·kg-1,sc)可以增加深睡眠和浅睡眠 ,减少觉醒 ;大剂量(0 375mg·kg-1,sc)则增加觉醒 ,减少全部睡眠成分。 5 HT2 受体拮抗剂ritanserin可以明显增加深睡眠 ,减少觉醒和REM睡眠。而 8 OH DPAT低剂量与ritanserin联合用药则使深浅睡眠明显增加 ,清醒和REM睡眠明显减少 ,具有协同作用。对于PCPA化使 3种睡眠成分均明显减少 ,觉醒比例明显增加的大鼠 ,ritanserin仅使浅睡眠增加其它成分不变。用 [3 H] ritanserin放射性配基结合显示 ,剥夺大鼠REM睡眠后皮层 5 HT2 受体Bmax值明显增加但Kd 值无变化 ;给予 5 HT1A激动剂 8 OH DPAT后皮层 5 HT2 受体Kd 和Bmax均降低。结论　 5 HT1A受体和 5 HT2 受体与睡眠有密切关系

Relationship between the function of 5-HT_(1A,2) receptors and waking-sleeping stages

AIM To study the effects of 5 HT 1A receptor agonist 8 OH DPAT and 5 HT 2 receptor antagonist ritanserin on wake and each stages of sleep, the binding capacity of 5 HT 2 receptor following administration of 5 HT 1A receptor agonist and REM sleep deprivation in rats, analyze the relationship between above serotonergic subreceptors and the role of 5 HT 2 receptor in sleep of rats. METHOD Using the auto analyzing system of sleep in rats to analyze quantitatively the changes of waking and sleeping stages,injection of PCPA inducing sleep deprivation, platform above water to deprive REM sleep in rats and radioligand receptor assay. RESULTS Administration of low dose (0 01 mg·kg -1 , sc) 8 OH DPAT could increase deep and light sleep,decrease wake time , while high dose (0 375 mg·kg -1 , sc) could increase wake time and decrease all of the sleeping stages. Ritanserin could significantly increase deep sleep, decrease wake and REM sleep time. A combination of low dose 8 OH DPAT and ritanserin could increase deep and light sleep, decrease wake and REM sleep more efficiently. Ritanserincant restore to normal sleep except light sleep in sleep deprived rats pretreated with PCPA. Observation of the changes in specific binding capacity of 5 HT 2 receptor in cortex under the two different conditions with [ 3H] ritanserin as ligand, after deprivation of REM sleep B max was increased significantly and K d had no change, while following administration of low and high dose 8 OH DPAT K d B max were markedly decreased. CONCLUSION There were relation between the both serotonergic subreceptors and sleep, activation of 5 HT 1A receptor with low dose agonist, and blocking of 5 HT 2 receptor could increase deep sleep, synergistic effects were shown on increasing deep sleep and decreasing REM sleep following combination low dose of 5 HT 1A receptor agonist with 5 HT 2 receptor antagonist.