Ervin G N, Schmitz S A, Nemeroff C B, Prange A J
Eur J Pharmacol. 1981 Jun 10;72(1):35-43. doi: 10.1016/0014-2999(81)90294-6.
We compared the arousal and hyperactivity produced by intraperitoneal (i.p.) injections of thyrotropin-releasing hormone (TRH, pGlu-His-Pri-NH2; 10, 20, 30 and 60 mg/kg) and 0.3 and 2 mg/kg d-amphetamine (low and moderate amph., respectively) by measuring the occurrence of discrete behavioral items with a behavioral sampling and scoring method. To minimize extraneous variables affecting activity, rats were caged singly inside isolated observation chambers and tested in the daytime after a 2.5 h period of habituation. Under these conditions, vehicle (0.9% NaCl)-treated rats were inactive and either rested or slept through 80% of all time samples taken in the hour after injection. Both TRH and amph. produced significant arousal from sleeping, but TRH, at all doses tested, produced less arousal than moderate amph. and a pattern of behavioral responses which differed from both low and moderate amph. Moderate amph. produced marked increase in forward locomotion and rearing, but low amph. and TRH did not. Both TRH and low amph. increased grooming (perhaps simply by increasing wakefulness), but TRH failed to increase sniffing, a cardinal feature of ampha.-induced excitement. Unlike amph., TRH produced wet-dog shakes, piloerection, tail elevation and teeth chattering. Both mod. amph. and TRH significantly produced increased activity when compared to controls as assessed with photocell counts, though the amph. effect was more robust. The lack of arousal after i.p. injections of thyroid-stimulating hormone (10 I.U./kg) or melanocyte-stimulating hormone release-inhibiting factor (Pro-Leu-Gly-NH2; 60 mg/kg) is evidence that TRH-induced arousal is neither mediated by activation of the pituitary-thyroid axis nor by a non-specific effect of tripeptides generally.
我们通过行为抽样和评分方法测量离散行为项目的发生情况，比较了腹腔注射促甲状腺激素释放激素（TRH，焦谷氨酸-组氨酸-脯氨酸-酰胺；10、20、30和60mg/kg）以及0.3和2mg/kg右旋苯丙胺（分别为低剂量和中剂量苯丙胺）所产生的觉醒和多动。为了尽量减少影响活动的外部变量，将大鼠单独关在隔离的观察室中，并在经过2.5小时适应期后的白天进行测试。在这些条件下，注射溶媒（0.9%氯化钠）的大鼠不活动，在注射后一小时内所采集的所有时间样本中，有80%的时间处于休息或睡眠状态。TRH和苯丙胺均可使大鼠从睡眠中显著觉醒，但在所有测试剂量下，TRH产生的觉醒程度均低于中剂量苯丙胺，且其行为反应模式与低剂量和中剂量苯丙胺均不同。中剂量苯丙胺可使向前运动和竖毛显著增加，但低剂量苯丙胺和TRH则无此作用。TRH和低剂量苯丙胺均可增加理毛行为（可能只是通过增加觉醒程度），但TRH未能增加嗅探行为，而嗅探是苯丙胺诱发兴奋的主要特征。与苯丙胺不同，TRH可引起湿狗样抖动、竖毛、尾巴翘起和牙齿打颤。与对照组相比，通过光电管计数评估发现，中剂量苯丙胺和TRH均显著增加了活动量，不过苯丙胺的作用更强。腹腔注射促甲状腺激素（10国际单位/千克）或促黑素细胞激素释放抑制因子（脯氨酸-亮氨酸-甘氨酸-酰胺；60mg/kg）后未出现觉醒，这证明TRH诱导的觉醒既不是由垂体-甲状腺轴的激活介导的，也不是由三肽的非特异性作用介导的。
