Leppävuori A, Putkonen P T
Brain Res. 1980 Jul 7;193(1):95-115. doi: 10.1016/0006-8993(80)90948-8.
Polygraphic 16 h sleep recording were carried out in 35 adult cats following i.p. injections of various alpha-adrenoceptors agonists, antagonists and their combinations. The direct alpha-agonists, clonidine (CLO 0.005, 0.01 and 0.02 mg/kg) and xylazine (XYL 0.5, 1 and 2 mg/kg), dose-dependently decreased paradoxical sleep (PS) and deep slow wave sleep (S2), with a respective increase mainly in drowsy waking (D). alpha-Methyldopa, precursor of the potent alpha-agonist, alpha-m-noradrenaline (alpha-m-NA) suppressed PS, with little effect on other vigilance stages. Of the alpha-antagonists only phentolamine (PHE 10 and 20 mg/kg) increased significantly the 16 h mean of PS. Thymoxamine (THY 5 mg/kg) gave a modest, temporary increment in PS between 4 and 8 h after the injection, but the effect diminished with 10 mg/kg THY. Yohimbine (YOH 2 mg/kg) induced an early increment in aroused waking (A). Tolazoline (TOL 6 mg/kg) and THY (5 and 10 mg/kg) increased D in the first 4 h epoch. Phenoxybenzamine (PBZ 10 mg/kg) significantly decreased the 16 h mean of S2 and PS. PHE antagonized the PS suppressing effect of CLO (0.01 mg/kg) already at the dose of 5 mg/kg and with 10 and 20 mg/kg its PS increasing character prevailed. TOL (6 mg/kg) and YOH (2 mg/kg) were also effective antagonists to CLO. THY (5 and 10 mg/kg) was ineffective in this respect and clearly potentiated the S2 inhibiting effect of CLO. PBZ (10 mg/kg) powerfully potentiated both PS and S2 suppressing effects of CLO. PHE (20 mg/kg) was tested against XYL (0.5 and 1 mg/kg) and alpha-methyldopa (100 mg/kg). It also antagonized the PS inhibiting action of these drugs. All the three agonists preferentially stimulate presynaptic (alpha 2) type of alpha-adrenoceptors, inhibitory to noradrenaline (NA) transmission. Furthermore, as only antagonists possessing presynaptic potency inhibited PS suppression by alpha 2-agonists, while preferential alpha 1-antagonists were either ineffective or potentiated this effect, the results favor the hypothesis of a positive involvement of NA in the mechanisms of PS. The optimal level of NA transmission for PS may, however, be postulated to lie below that for arousal, in which case the balanced blockade of alpha 1- and alpha 2-adrenoceptors by PHE might be exceptionally favorable to PS. The possible role of alpha-adrenoceptive influences on cholinergic and 5-HT neurons and their relevance to alpha 2-agonist-induced sedation and inhibition of PS and S2 are discussed.
对35只成年猫进行腹腔注射各种α-肾上腺素能受体激动剂、拮抗剂及其组合后，进行了16小时的多导睡眠记录。直接α-激动剂可乐定（CLO，0.005、0.01和0.02mg/kg）和赛拉嗪（XYL，0.5、1和2mg/kg）剂量依赖性地减少异相睡眠（PS）和深度慢波睡眠（S2），主要分别增加昏昏欲睡的觉醒（D）。α-甲基多巴是强效α-激动剂α-间去甲肾上腺素（α-m-NA）的前体，可抑制PS，对其他警觉阶段影响较小。在α-拮抗剂中，只有酚妥拉明（PHE，10和20mg/kg）显著增加了16小时的PS平均值。噻吗洛尔（THY，5mg/kg）在注射后4至8小时使PS有适度的暂时增加，但10mg/kg的THY时效果减弱。育亨宾（YOH，2mg/kg）引起觉醒（A）的早期增加。妥拉唑啉（TOL，6mg/kg）和THY（5和10mg/kg）在最初4小时内增加D。酚苄明（PBZ，10mg/kg）显著降低16小时的S2和PS平均值。PHE在5mg/kg剂量时就拮抗了CLO（0.01mg/kg）对PS的抑制作用，10和20mg/kg时其增加PS的特性占主导。TOL（6mg/kg）和YOH（2mg/kg）也是CLO的有效拮抗剂。THY（5和10mg/kg）在这方面无效，且明显增强了CLO对S第二阶段的抑制作用。PBZ（10mg/kg）有力地增强了CLO对PS和S2的抑制作用。测试了PHE（20mg/kg）对抗XYL（0.5和1mg/kg）和α-甲基多巴（100mg/kg）的作用。它也拮抗了这些药物对PS的抑制作用。所有这三种激动剂优先刺激对去甲肾上腺素（NA）传递有抑制作用的突触前（α2）型α-肾上腺素能受体。此外，由于只有具有突触前效力的拮抗剂抑制α2-激动剂对PS的抑制，而优先的α1-拮抗剂要么无效要么增强这种作用，结果支持NA在PS机制中起积极作用的假说。然而，可以假定PS的NA传递最佳水平低于觉醒的水平，在这种情况下，PHE对α1-和α2-肾上腺素能受体的平衡阻断可能对PS特别有利。讨论了α-肾上腺素能影响对胆碱能和5-羟色胺神经元的可能作用及其与α2-激动剂诱导的镇静以及对PS和S2的抑制的相关性。
