Sircar Ratna, Soliman Karam F A
Developmental Neuroscience Laboratory, Department of Psychiatry and Behavioral Sciences, Albert Einstein College of Medicine, Bronx, NY 10461, USA.
Pharmacol Biochem Behav. 2003 Mar;74(4):943-52. doi: 10.1016/s0091-3057(03)00025-x.
Exposing the developing brain to the N-methyl-D-aspartate (NMDA) receptor antagonist phencyclidine (PCP) has been shown to cause deficits in neurobehavioral functions, particularly on learning and memory and seizure sensitivity. Besides acting as a noncompetitive NMDA antagonist, PCP at high doses is known to affect the dopaminergic system. The present study assessed the effect of postnatal PCP treatment on locomotor activity and striatal dopamine (DA) D(2) receptor. Male and female rat pups were injected intraperitoneally (i.p.) with one of three doses of PCP (1, 3 and 5 mg/kg) or saline from postnatal day (PD) 5 to PD 15. Control and PCP-treated rats were given a challenge dose of PCP (10 mg/kg) as adults, and their locomotor behaviors--locomotion, stereotypy and ataxia--were scored. Postnatal PCP treatment did not have any significant effect in either sex on any of the PCP-induced locomotor behavioral paradigms studied. Separate groups of male and female rats were treated daily with saline or PCP (5 mg/kg i.p.) from PD 5 to PD 15 and sacrificed either as juveniles (PD 21) or adults, and D(2) receptor binding was measured in their striata. Striatal D(2) receptor density in juvenile and adult male postnatal PCP-treated rats did not differ from saline-treated controls. Adult female PCP-treated rats showed a slight but significant reduction in the maximal binding of striatal D(2) receptors. There was no effect of postnatal PCP on striatal D(2) receptor binding in female juvenile rats. These results support the hypothesis that blocking the developing NMDA receptor minimally affects PCP-induced locomotor behavior and the striatal D(2) receptor.
已表明，将发育中的大脑暴露于N-甲基-D-天冬氨酸（NMDA）受体拮抗剂苯环利定（PCP）会导致神经行为功能缺陷，尤其是在学习、记忆和癫痫易感性方面。除了作为非竞争性NMDA拮抗剂外，高剂量的PCP还已知会影响多巴胺能系统。本研究评估了产后PCP治疗对运动活动和纹状体多巴胺（DA）D（2）受体的影响。从出生后第5天（PD）至第15天，给雄性和雌性幼鼠腹腔注射（i.p.）三种剂量之一的PCP（1、3和5mg/kg）或生理盐水。将对照和PCP处理的大鼠作为成年鼠给予一次PCP激发剂量（10mg/kg），并对它们的运动行为——运动、刻板行为和共济失调进行评分。产后PCP治疗对所研究的任何PCP诱导的运动行为范式在两性中均无显著影响。将单独的雄性和雌性大鼠组从PD 5至PD 15每天用生理盐水或PCP（5mg/kg i.p.）处理，并在幼年（PD 21）或成年时处死，然后测量其纹状体中的D（2）受体结合。产后接受PCP治疗的幼年和成年雄性大鼠的纹状体D（2）受体密度与生理盐水处理的对照组无差异。成年雌性PCP处理的大鼠纹状体D（2）受体的最大结合略有但显著降低。产后PCP对雌性幼年大鼠的纹状体D（2）受体结合没有影响。这些结果支持以下假设：阻断发育中的NMDA受体对PCP诱导的运动行为和纹状体D（2）受体的影响最小。
