Scalzo F M, Burge L J
Arkansas Children's Hospital Research Institute, Little Rock 72202.
Neurotoxicology. 1994 Spring;15(1):191-200.
To determine the role of NMDA receptor blockade and sigma receptors in the behavioral effects of PCP during development, we assessed the behavioral effects of PCP, (+)-MK-801 and 1,3-Di(2-tolyl)guanidine (DTG) in preweanling rats. In the first experiment, rats were injected sc on postnatal day (PND) 19 with 0.5-4.5 mg/kg PCP, and locomotor activity and wall climbing behavior were scored. PCP induced high levels of locomotor activity on PND 19 in a dose dependent manner with the 2.0 mg/kg dose producing the greatest activity. In the second experiment, rats were injected on PND 12 or 19 with 1.0-4.0 mg/kg PCP or 0.1-0.4 mg/kg (+)-MK-801 and tested using the same procedures. Both PCP and (+)-MK-801 induced activity increases on PND 19 in a dose dependent manner, with 2.0 and 3.0 mg/kg PCP and 0.2 mg/kg (+)-MK-801 inducing the highest activity levels. Peak activity levels on PND 12 were approximately 30% of those observed on PND 19, with the lowest dose of PCP and (+)-MK-801 producing the greatest activity. Large amounts of wall climbing behavior were elicited by PCP on PND 12, whereas (+)-MK-801 induced only minor amounts of wall climbing. In the third experiment, the effects of 0, 1, 3, 6, or 12 mg/kg DTG were examined in PND 13-14 and 16-17 rats. DTG had little effect on locomotor activity on PND 13-14, although the highest dose did inhibit activity. On PND 16-17, all doses of DTG tended to increase locomotor activity. The results suggest (1) the robust locomotor effects of PCP on PND 19 are mediated in part by NMDA mechanisms (2) this period of increased sensitivity to both PCP and (+)-MK-801 might represent a critical period of development when systems mediating locomotor activity are vulnerable to neurotoxic insult (3) NMDA blockade alone does not mediate PCP-induced wall climbing behavior and (4) that at the doses of DTG and the ages tested, sigma receptors do not play a role in the locomotor-inducing effects of PCP.
为了确定N-甲基-D-天冬氨酸（NMDA）受体阻断和σ受体在发育过程中苯环己哌啶（PCP）行为效应中的作用，我们评估了PCP、（+）-MK-801和1,3-二（2-甲苯基）胍（DTG）对断奶前大鼠的行为影响。在第一个实验中，于出生后第19天（PND19）给大鼠皮下注射0.5 - 4.5mg/kg的PCP，并对其运动活性和爬壁行为进行评分。PCP在PND19上以剂量依赖性方式诱导高水平的运动活性，2.0mg/kg剂量产生的活性最高。在第二个实验中，于PND12或19给大鼠注射1.0 - 4.0mg/kg的PCP或0.1 - 0.4mg/kg的（+）-MK-801，并使用相同程序进行测试。PCP和（+）-MK-801在PND19上均以剂量依赖性方式诱导活性增加，2.0和3.0mg/kg的PCP以及0.2mg/kg的（+）-MK-801诱导的活性水平最高。PND12上的峰值活性水平约为PND19上观察到的30%，最低剂量的PCP和（+）-MK-801产生的活性最大。PCP在PND12上引发大量爬壁行为，而（+）-MK-801仅诱导少量爬壁行为。在第三个实验中，研究了0、1、3、6或12mg/kg DTG对PND13 - 14和16 - 17大鼠的影响。DTG在PND13 - 14上对运动活性影响较小，尽管最高剂量确实抑制了活性。在PND16 - 17上，所有剂量的DTG都倾向于增加运动活性。结果表明：（1）PCP在PND19上强大的运动效应部分由NMDA机制介导；（2）对PCP和（+）-MK-801敏感性增加的这一时期可能代表发育的关键时期，此时介导运动活性的系统易受神经毒性损伤；（3）单独的NMDA阻断并不介导PCP诱导的爬壁行为；（4）在所测试的DTG剂量和年龄下，σ受体在PCP诱导运动的效应中不起作用。
