ToxSci Advance Access originally published online on July 30, 2008
Toxicological Sciences 2008 106(1):172-179; doi:10.1093/toxsci/kfn152
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Published by Oxford University Press 2008.
Neonatal PCP Is More Potent than Ketamine at Modifying Preweaning Behaviors of Sprague-Dawley Rats
Department of Interdisciplinary Biomedical Sciences, University of Arkansas for Medical Sciences, Little Rock, Arkansas 72205; and Division of Neurotoxicology, National Center for Toxicological Research/US Food and Drug administration, Jefferson, Arkansas 72079
1 To whom correspondence should be addressed at Division of Neurotoxicology, National Center for Toxicological Research/FDA, 3900 NCTR Drive, Jefferson, AR 72079. Fax 870-543-7181. E-mail: sherry.ferguson{at}fda.hhs.gov.
Received May 2, 2008; accepted July 10, 2008
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Abstract |
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Treatment with N-methyl-D-aspartate (NMDA) receptor antagonists, such as ketamine (KET) or phencyclidine (PCP), can trigger apoptotic neurodegeneration in neonatal rodents; however, little is known about the behavioral alterations resulting from such treatment. Here, rats were sc treated with saline; 10 mg/kg PCP on postnatal days (PNDs) 7, 9, and 11; 20 mg/kg KET (six injections every 2 h on PND 7); or a regimen of ketamine and 250 mg/kg L-carnitine (KLC) both administered on PND 7 with additional 250 mg/kg doses of L-carnitine given on PNDs 8–11. Postinjection, the home cage behavior of each pup was categorized on PNDs 7–11. Slant board and forelimb hang behaviors were examined on PNDs 8–11 and 12–16, respectively. The initial KET or KLC injections on PND 7 elevated abnormal home cage activity (i.e., paresis and paddling); however, KLC pup behavior returned to normal by the fourth injection, indicating the protective effects of L-carnitine against NMDA antagonist toxicity. PCP treatment caused substantial abnormal home cage activity on each injection day (PNDs 7, 9, and 11). Latencies to turn on the slant board were significantly longer on PND 8 for KET- and PCP-treated pups and PND 10 for PCP-treated pups. On PND 12, the forelimb hang time of PCP-treated pups was significantly shorter. Body weight was decreased on PNDs 8–18 in PCP-treated pups and PNDs 8–10 in KET-treated pups. These data indicate that developmental NMDA antagonist treatment causes short-term behavioral alterations which appear related to motor coordination and may be cerebellar in nature. Furthermore, single PCP injections appear more potent at altering behavior than multiple injections of KET.
Key Words: ketamine; phencyclidine; neurodegeneration; forelimb hang; negative geotaxis; pup behavior.