Rocha J B, Rocha L K, Emanuelli T, Pereira M E
Departamento de Química, Centro de Ciências Naturais e Exatas, Universidade Federal de Santa Maria, Campus Universitario-Camobi 97105-900, RS, Santa Maria, Brazil.
Toxicol Lett. 2001 Dec 15;125(1-3):143-50. doi: 10.1016/s0378-4274(01)00435-0.
During the early post-natal period the brain is extremely sensitive to external agents. In the present study, we examined the effects of the treatment with lead acetate (3.5 or 7.0 mg/kg) and mercuric chloride (2.5 or 5.0 mg/kg) during the early post-natal period (day 8-12) on the behavioral response to chlorpromazine (CPZ) of 22-day-old rats. The effects of these metals on the sulfhydryl-containing enzyme delta-aminolevulinate dehydratase (delta-ALA-D) were also investigated. Mercuric chloride (2.5 mg/kg) did not affect brain enzyme activity, but caused a significant stimulation of renal delta-ALA-D of 24-day-old rats (27%), while animals treated with 5 mg/kg HgCl(2) showed a small but significant inhibition of cerebral (10%) and renal delta-ALA-D activity (15%). Lead acetate (3.5 or 7 mg/kg) treatment did not affect renal or cerebral delta-ALA-D. Mercuric chloride treatment (5 mg/kg) changed the pattern of open-field activity and the CPZ-induced catalepsy. However, since the undernutrition that accompanied the metal treatment also caused changes in CPZ-induced catalepsy, the effect of mercury on catalepsy could not be clearly established. Lead acetate treatment (7 mg/kg) changed the pattern of open-field motor activity and abolished the decrease in activity observed in control rats. The cataleptic response of animals to CPZ was also affected by lead acetate treatment (7 mg/kg). The increase in activity is compatible with the hyperactivity described in animals exposed to lead for long periods. Thus, the present study suggests that a short exposure to lead or mercury during suckling (second stage of rapid post-natal brain growth) caused permanent changes in locomotor activity that can be interpreted as hyperactivity. Additionally, the behavioral response to CPZ was affected by metal treatment indicating an alteration in the dopaminergic system.
在出生后的早期阶段,大脑对外部因素极为敏感。在本研究中,我们检测了出生后早期(第8 - 12天)用醋酸铅(3.5或7.0毫克/千克)和氯化汞(2.5或5.0毫克/千克)处理对22日龄大鼠对氯丙嗪(CPZ)行为反应的影响。还研究了这些金属对含巯基酶δ-氨基乙酰丙酸脱水酶(δ-ALA-D)的影响。氯化汞(2.5毫克/千克)不影响脑酶活性,但可显著刺激24日龄大鼠肾脏的δ-ALA-D(升高27%),而用5毫克/千克HgCl₂处理的动物脑(降低10%)和肾脏δ-ALA-D活性(降低15%)有轻微但显著的抑制。醋酸铅(3.5或7毫克/千克)处理不影响肾脏或脑的δ-ALA-D。氯化汞处理(5毫克/千克)改变了旷场活动模式以及CPZ诱导的僵住症。然而,由于金属处理伴随的营养不良也导致CPZ诱导的僵住症发生变化,汞对僵住症的影响无法明确确定。醋酸铅处理(7毫克/千克)改变了旷场运动活动模式,并消除了对照大鼠中观察到的活动减少。醋酸铅处理(7毫克/千克)也影响了动物对CPZ的僵住症反应。活动增加与长期接触铅的动物中描述的多动相符。因此,本研究表明,在哺乳期间(出生后大脑快速生长的第二阶段)短期接触铅或汞会导致运动活动的永久性变化,可解释为多动现象。此外,金属处理影响了对CPZ的行为反应,表明多巴胺能系统发生了改变。