Balduini W, Cimino M, Lombardelli G, Abbracchio M P, Peruzzi G, Cecchini T, Gazzanelli G C, Cattabeni F
Clin Neuropharmacol. 1986;9 Suppl 3:S8-18.
The administration of the antimitotic compound methylazoxymethanol (MAM) to gestating rats induces a dose-dependent atrophy of specific brain areas in the offspring. This specificity is strictly dependent upon the time of MAM administration. When given at day 15 of gestation only the cortex, hippocampus, and striatum are affected, whereas when given to rat pups at postnatal day 1, the atrophy is apparent only in the cerebellum. The microencephalic offspring of dams treated at day 15 of gestation develop normally to adulthood, without manifest signs of this profound telencephalic contraction. Behavioral abnormalities are observable when subjecting these animals to tests that involve learning. The deficit in associative behavior might have its anatomical and neurochemical counterpart in the disruption of the neuronal circuitry in the neocortex, where about 50% of interneurons are absent in layers II-IV after a dose of MAM of 25 mg/kg. Loss of intrinsic neurons occurs also in the striatum, as revealed by neurochemical and pharmacological analysis. Indeed, MAM rats show a reduced dopamine-dependent adenylate cyclase activity and a reduced motor stimulation in response to dopaminergic stimulants. MAM rats are therefore an interesting animal model of chronic brain damage induced transplacentally, which could serve for studying adaptive mechanisms of the CNS to this damage and its pharmacological manipulation.
给妊娠大鼠注射抗有丝分裂化合物甲基偶氮甲醇（MAM）会导致后代特定脑区出现剂量依赖性萎缩。这种特异性严格取决于MAM给药的时间。在妊娠第15天给药时，只有皮质、海马体和纹状体受到影响，而在出生后第1天给幼鼠给药时，萎缩仅在小脑中明显。在妊娠第15天接受治疗的母鼠所生的小头畸形后代正常发育至成年，没有明显的这种严重端脑收缩迹象。当对这些动物进行涉及学习的测试时，可以观察到行为异常。联想行为的缺陷可能在新皮质神经元回路的破坏中具有其解剖学和神经化学对应物，在给予25mg/kg剂量的MAM后，新皮质的II-IV层中约50%的中间神经元缺失。神经化学和药理学分析表明，纹状体中也会出现内在神经元的丧失。事实上，MAM大鼠表现出多巴胺依赖性腺苷酸环化酶活性降低以及对多巴胺能刺激物的运动刺激反应降低。因此，MAM大鼠是一种通过胎盘诱导慢性脑损伤的有趣动物模型，可用于研究中枢神经系统对这种损伤的适应性机制及其药理学调控。
