Hayashi T, Kunihara M, Tadokoro S
Jpn J Pharmacol. 1987 Jan;43(1):17-25. doi: 10.1254/jjp.43.17.
Male neonates of Wistar strain rats were given s.c. 1-4 mg/kg/day of methamphetamine (MAP) for 7 successive days from days 6 to 12 after birth. The acquisition processes of the discriminative lever-press avoidance response were investigated from day 60 after birth. Effects of the postnatal pretreatments with MAP on saturation constants for specific bindings of 3H-spiperone (SPP) and 3H-WB4101, respectively, in 8 brain regions were also investigated at 100-120 days after birth. In addition, dopamine, noradrenaline and the levels of their metabolites were measured in the brain. No significant difference was detected in body weight, gross behaviors and avoidance learning between saline- and MAP-pretreated groups. However, effects of MAP and apomorphine on the locomotor activity significantly increased in the MAP-pretreated group. Significant decreases in Bmax and Kd values of 3H-SPP binding sites in the striatum were detected in the MAP-pretreated group, while significant decreases in Bmax values of 3H-WB4101 binding sites in the cortex and hippocampus as well as those in Kd values in the hippocampus were found in the treated group. Dopamine and noradrenaline levels significantly decreased in the MAP-pretreated group, but on the contrary, their metabolites levels significantly increased. These results suggest that postnatal pretreatments with MAP produce long-lasting behavioral changes associated with an impaired development of catecholaminergic neurons in the rat brain after maturity.
将出生后6至12天的Wistar品系雄性新生大鼠，连续7天皮下注射1 - 4毫克/千克/天的甲基苯丙胺（MAP）。从出生后第60天开始研究辨别性杠杆按压回避反应的习得过程。还在出生后100 - 120天研究了出生后用MAP预处理对大鼠8个脑区中3H-螺哌隆（SPP）和3H-WB4101特异性结合饱和常数的影响。此外，还测量了脑中多巴胺、去甲肾上腺素及其代谢产物的水平。盐水预处理组和MAP预处理组在体重、总体行为和回避学习方面未检测到显著差异。然而，MAP预处理组中MAP和阿扑吗啡对运动活动的影响显著增加。MAP预处理组纹状体中3H-SPP结合位点的Bmax和Kd值显著降低，而处理组中皮质和海马体中3H-WB4101结合位点的Bmax值以及海马体中Kd值均显著降低。MAP预处理组中多巴胺和去甲肾上腺素水平显著降低，但相反，它们的代谢产物水平显著升高。这些结果表明，出生后用MAP预处理会产生长期的行为变化，这与成熟后大鼠脑中儿茶酚胺能神经元发育受损有关。
