Nabeshima T, Noda Y, Itoh K, Kameyama T
Department of Chemical Pharmacology, Faculty of Pharmaceutical Sciences, Meijo University, Nagoya, Japan.
Pharmacol Biochem Behav. 1988 Oct;31(2):405-9. doi: 10.1016/0091-3057(88)90366-8.
The role of cholinergic and GABAergic neuronal systems on the cycloheximide (CXM)-induced amnesia was investigated using the step-down-type passive avoidance task in mice. CXM (7.5-120 mg/kg, SC) given just after the training caused amnesia (indicated by short latency to step down from the platform on the grid floor) in the retention test conducted 24 hr later in a dose-dependent fashion. In the CXM (60 mg/kg)-treated mice, a choline esterase inhibitor, physostigmine (PHY; 0.125 and 0.25 mg/kg, IP), or GABA agonists, muscimol (1 and 2 mg/kg, IP) and baclofen (6 and 12 mg/kg, IP), given just after training markedly prolonged step down latency (SDL), indicating reversal of amnesia. The antiamnesic action of PHY (0.125 mg/kg) was almost completely antagonized by a central acetylcholine antagonist, scopolamine (3 mg/kg, SC), but not by a peripheral acetylcholine antagonist, butylscopolamine (3 mg/kg, SC). Furthermore, the antiamnesic action of muscimol (2 mg/kg) was reversed by GABA antagonists, picrotoxin (0.5 mg/kg, SC) and bicuculline (0.5 mg/kg, SC), while the effect of baclofen (12 mg/kg) was reversed by picrotoxin (0.5 mg/kg), but not by bicuculline (0.5 mg/kg). These results suggest that the dysfunction of cholinergic and GABAergic neuronal systems play an important role in the CXM-induced memory impairment on the passive avoidance task.
采用小鼠跳台型被动回避任务，研究胆碱能和γ-氨基丁酸能（GABAergic）神经元系统在环己酰亚胺（CXM）诱导的失忆中的作用。训练后立即皮下注射CXM（7.5 - 120 mg/kg），在24小时后进行的记忆保持测试中，以剂量依赖的方式导致失忆（表现为从网格地板上的平台跳下的潜伏期缩短）。在接受CXM（60 mg/kg）处理的小鼠中，训练后立即腹腔注射胆碱酯酶抑制剂毒扁豆碱（PHY；0.125和0.25 mg/kg）或GABA激动剂蝇蕈醇（1和2 mg/kg）和巴氯芬（6和12 mg/kg），显著延长了跳下潜伏期（SDL），表明失忆得到逆转。PHY（0.125 mg/kg）的抗失忆作用几乎完全被中枢乙酰胆碱拮抗剂东莨菪碱（3 mg/kg，皮下注射）拮抗，但未被外周乙酰胆碱拮抗剂丁溴东莨菪碱（3 mg/kg，皮下注射）拮抗。此外，蝇蕈醇（2 mg/kg）的抗失忆作用被GABA拮抗剂印防己毒素（0.5 mg/kg，皮下注射）和荷包牡丹碱（0.5 mg/kg，皮下注射）逆转，而巴氯芬（12 mg/kg）的作用被印防己毒素（0.5 mg/kg）逆转，但未被荷包牡丹碱（0.5 mg/kg）逆转。这些结果表明，胆碱能和GABA能神经元系统功能障碍在CXM诱导的被动回避任务记忆损害中起重要作用。
