Effects of postnatal PCP treatment on locomotor behavior and striatal D2 receptor.
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.
Sircar
Ratna
R
Developmental Neuroscience Laboratory, Department of Psychiatry and Behavioral Sciences, Albert Einstein College of Medicine, Bronx, NY 10461, USA. sircar@aecom.yu.edu
Soliman
Karam F A
KF
D000818:Animals; D000831:Animals, Newborn; D001259:Ataxia / Q000139:chemically induced / Q000378:metabolism; D003342:Corpus Striatum / Q000187:drug effects* / Q000378:metabolism; D005260:Female; D008297:Male; D009043:Motor Activity / Q000187:drug effects* / Q000502:physiology; D010622:Phencyclidine / Q000378:metabolism / Q000494:pharmacology* / Q000633:toxicity; D011247:Pregnancy; D011485:Protein Binding / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D017448:Receptors, Dopamine D2 / Q000378:metabolism*; D013239:Stereotyped Behavior / Q000187:drug effects / Q000502:physiology
D017448:Receptors, Dopamine D2; D010622:Phencyclidine