Effect of repeated administration of phencyclidine on spatial performance in an eight-arm radial maze with delay in rats and mice.
Phencyclidine (PCP) is an N-methyl-D-aspartate (NMDA) glutamate receptor channel noncompetitive antagonist that produces some of the symptoms of schizophrenia, including delusions, hallucinations, and negative symptoms as well as cognitive impairment. Thus, administration of PCP to rodents and nonhuman primates has been suggested to provide a potential animal model for schizophrenia. There have been some reports that 7-14 days of PCP administration can bring about enduring impairments in working memory in rodents but not all studies have been consistent in this regard. The present study determined whether repeated PCP administration impaired spatial performance in rats or mice trained to make minimal errors in an eight-arm radial maze task with a delay. Male Sprague-Dawley rats and C57BL/6J mice received 14 daily injection of vehicle or PCP (10 mg/kg, s.c.) followed by a withdrawal period of 1 week. The number of arm reentry errors and the distance traveled to complete the task were not significantly different between PCP-treated and vehicle-treated rats on 2, 8, and 14 days of PCP administration or 8 days following withdrawal of PCP. Mice treated with PCP for up to 2 weeks also had no significant differences in the number of arm reentry errors, travel distances, the numbers of visits to different arms during the first eight choices, or latencies to take all eight pellets compared to the vehicle-treated group. Thus, the present study failed to demonstrate that repeated administration of PCP to rats or mice produces enduring memory impairment. Factors potentially contributing to the discrepancies between various studies are discussed.
Li
Zhu
Z
Division of Psychopharmacology, Departments of Psychiatry and Pharmacology, Vanderbilt University School of Medicine, Nashville, TN, USA. zhi.li@vanderbilt.edu
Kim
Chan H
CH
Ichikawa
Junji
J
Meltzer
Herbert Y
HY
D000818:Animals; D018691:Excitatory Amino Acid Antagonists / Q000008:administration & dosage / Q000494:pharmacology*; D007091:Image Processing, Computer-Assisted; D008297:Male; D018782:Maze Learning / Q000187:drug effects*; D008568:Memory / Q000187:drug effects; D051379:Mice; D008810:Mice, Inbred C57BL; D010622:Phencyclidine / Q000008:administration & dosage / Q000494:pharmacology*; D011597:Psychomotor Performance / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D013028:Space Perception / Q000187:drug effects*; D013045:Species Specificity; D013997:Time Factors
D018691:Excitatory Amino Acid Antagonists; D010622:Phencyclidine