Sircar R, Veliskova J, Moshe S L
Department of Psychiatry, Albert Einstein College of Medicine/Montefiore Medical Center, Bronx, NY 10461.
Brain Res Dev Brain Res. 1994 Sep 16;81(2):185-91. doi: 10.1016/0165-3806(94)90305-0.
Although excitatory amino acids are known to play a critical role in the plasticity of developing brain, the behavioral effects of blocking the N-methyl-D-aspartate (NMDA) receptor-gated ion channel during development are not clear. Here we report the effects of chronic postnatal administration of 1-phenylcyclohexylpiperidine (phencyclidine or PCP), a NMDA channel blocker, on seizure susceptibility. To study the short-term effects of chronic PCP administration on pentylenetetrazol (PTZ)-induced seizures, rats were treated with PCP (5 mg/kg, i.p.) for 11 days from postnatal days 5-15, 24-34 or 44-54 and tested in the PTZ-induced seizure paradigm on postnatal days 21, 40 and 60, respectively. Administration of PCP in 5-15-day-old rats resulted in increased seizure susceptibility at day 21, while administration of PCP in postweanling rats (days 24-34) markedly attenuated their susceptibility to seizures at day 40. PCP injection had little effect on the seizure susceptibility of older rats. To study the long-term effects of postnatal PCP treatment, rats were injected with PCP (5 mg/kg from postnatal day 5-15, i.p.) and were tested for PTZ-induced seizures on postnatal days 40 and 60; each rat was tested only once. When tested for PTZ-induced seizure on day 40, PCP-treated rats did not differ from saline-treated controls. When tested on day 60, PCP-treated rats had a lower incidence of seizures and in the rats that did have seizures their latencies were significantly prolonged compared to controls. Together, our data suggest that chronic PCP administration alters PTZ-induced seizure susceptibility in an age-dependent manner and chronic PCP administration in postnatal rats produces long-term changes that persist into adulthood.
虽然已知兴奋性氨基酸在发育中的大脑可塑性中起关键作用，但在发育过程中阻断N-甲基-D-天冬氨酸（NMDA）受体门控离子通道的行为影响尚不清楚。在此，我们报告了NMDA通道阻滞剂1-苯基环己基哌啶（苯环利定或PCP）在出生后长期给药对癫痫易感性的影响。为了研究慢性PCP给药对戊四氮（PTZ）诱导癫痫发作的短期影响，从出生后第5 - 15天、24 - 34天或44 - 54天开始，对大鼠腹腔注射PCP（5 mg/kg），持续11天，并分别在出生后第21天、40天和60天进行PTZ诱导癫痫发作的测试。在出生后5 - 15天的大鼠中给予PCP会导致在第21天癫痫易感性增加，而在断奶后大鼠（24 - 34天）中给予PCP则在第40天显著降低了它们对癫痫发作的易感性。PCP注射对老年大鼠的癫痫易感性影响不大。为了研究出生后PCP治疗的长期影响，大鼠在出生后第5 - 15天腹腔注射PCP（5 mg/kg），并在出生后第40天和60天进行PTZ诱导癫痫发作的测试；每只大鼠仅测试一次。在第40天进行PTZ诱导癫痫发作测试时，PCP处理的大鼠与生理盐水处理的对照组没有差异。在第60天进行测试时，PCP处理的大鼠癫痫发作发生率较低，并且在确实发生癫痫发作的大鼠中，其发作潜伏期与对照组相比显著延长。总之，我们的数据表明，慢性PCP给药以年龄依赖性方式改变PTZ诱导的癫痫易感性，并且在出生后大鼠中慢性PCP给药会产生持续到成年期的长期变化。
