Asakura W, Matsumoto K, Ohta H, Watanabe H
Division of Pharmacology, Toyama Medical and Pharmaceutical University, Japan.
Pharmacol Biochem Behav. 1994 Sep;49(1):79-84. doi: 10.1016/0091-3057(94)90459-6.
Effect of monoamine depletion on the REM sleep (REMs) deprivation-induced increase in clonidine response in the forced swimming test was investigated. Mice were deprived of REMs by the small pedestal method. Clonidine HCl (10-1000 micrograms/kg, IP), an alpha 2-adrenoceptor agonist, dose dependently increased swimming activities in group-housed and socially isolated mice used as the control groups. The dose-response relationship shifted to the left following REMs deprivation (ED50 values in the group-housed, isolated, and REMs-deprived mice were 250, 200, and 27 micrograms/kg, respectively). Monoamine depletion, induced by reserpine (5 mg/kg, IP) plus alpha-methyl-p-tyrosine (250 mg/kg, IP), did not produce any changes in the effects of clonidine in the control groups. However, in REMs-deprived mice, monoamine depletion significantly decreased the effect of 100 micrograms/kg clonidine, but not that of 300 micrograms/kg clonidine on swimming activity. These results indicate that clonidine-induced increase in swimming activity in the forced swimming test is mainly mediated by postsynaptic alpha 2-adrenoceptor, and that endogenous noradrenaline in the brain plays an important role in the increase of clonidine response following REMs deprivation treatment. The neuronal mechanism of the increase in clonidine response is discussed.
研究了单胺耗竭对快速眼动睡眠（REMs）剥夺诱导的强迫游泳试验中可乐定反应增加的影响。通过小平台法剥夺小鼠的快速眼动睡眠。α2-肾上腺素能受体激动剂盐酸可乐定（10 - 1000微克/千克，腹腔注射）剂量依赖性地增加了作为对照组的群居和社会隔离小鼠的游泳活动。快速眼动睡眠剥夺后剂量-反应关系向左移动（群居、隔离和快速眼动睡眠剥夺小鼠的ED50值分别为250、200和27微克/千克）。利血平（5毫克/千克，腹腔注射）加α-甲基-对酪氨酸（250毫克/千克，腹腔注射）诱导的单胺耗竭在对照组中对可乐定的作用未产生任何变化。然而，在快速眼动睡眠剥夺的小鼠中，单胺耗竭显著降低了100微克/千克可乐定对游泳活动的作用，但未降低300微克/千克可乐定的作用。这些结果表明，可乐定在强迫游泳试验中诱导的游泳活动增加主要由突触后α2-肾上腺素能受体介导，并且脑中内源性去甲肾上腺素在快速眼动睡眠剥夺处理后可乐定反应增加中起重要作用。讨论了可乐定反应增加的神经元机制。
