Watanabe T, Matsuhashi K, Takayama S
Nihon Yakurigaku Zasshi. 1985 Feb;85(2):79-90. doi: 10.1254/fpj.85.79.
The drugs used were methamphetamine, reserpine, norepinephrine, epinephrine, propranolol, chlorpromazine, haloperidol, pilocarpine and atropine. Each drug except for reserpine (days 7-13 and 14-19 of gestation) was administered subcutaneously to dams from day 7 to 19 of gestation. The body weight gain of dams receiving reserpine (days 7-13) and haloperidol was inhibited during the gestation period. Two out of 9 dams receiving methamphetamine died on day 21 of gestation period; However, no effect was observed in dams given other drugs. The body weight gain of pups was inhibited in methamphetamine and haloperidol treated groups. The mortality of pups was comparable in all groups. The behavioral development of the righting reflex, cliff drop avoidance and negative geotaxis of pups given reserpine (days 7-13), norepinephrine, chlorpromazine and haloperidol was significantly retarded in comparison with that of control pups. The spontaneous motor activity of pups measured by Animex was increased in reserpine (days 7-13) and epinephrine treated groups and decreased in the chlorpromazine treated group on day 28 postpartum, but comparable in all groups on day 56 postpartum. The conditioned avoidance responses using the shuttle box revealed deficits of avoidance learning of pups in the reserpine (days 7-13), norepinephrine and atropine treated groups. These findings suggest that the prenatal exposure to drugs acting on the autonomic nervous system may produce adverse effects on the behavioral development of pups; However, the adverse effects were more apparent by postnatal exposure than by prenatal exposure.
所使用的药物有甲基苯丙胺、利血平、去甲肾上腺素、肾上腺素、普萘洛尔、氯丙嗪、氟哌啶醇、毛果芸香碱和阿托品。除利血平(妊娠第7 - 13天和第14 - 19天)外,每种药物均在妊娠第7天至第19天皮下注射给母鼠。接受利血平(第7 - 13天)和氟哌啶醇的母鼠在妊娠期体重增加受到抑制。9只接受甲基苯丙胺的母鼠中有2只在妊娠期第21天死亡;然而,给予其他药物的母鼠未观察到影响。甲基苯丙胺和氟哌啶醇治疗组幼崽的体重增加受到抑制。所有组幼崽的死亡率相当。与对照幼崽相比,接受利血平(第7 - 13天)、去甲肾上腺素、氯丙嗪和氟哌啶醇的幼崽的翻正反射、悬崖回避和负趋地性的行为发育明显延迟。产后第28天,用Animex测量的利血平(第7 - 13天)和肾上腺素治疗组幼崽的自发运动活动增加,氯丙嗪治疗组减少,但产后第56天所有组相当。使用穿梭箱的条件回避反应显示,利血平(第7 - 13天)、去甲肾上腺素和阿托品治疗组的幼崽存在回避学习缺陷。这些发现表明,产前接触作用于自主神经系统的药物可能对幼崽的行为发育产生不利影响;然而,产后接触比产前接触的不利影响更明显。