The Effects of Early Postnatal PCP Administration on Performance in Locomotor Activity, Reference Memory, and Working Memory Tasks in C57BL/6 Mice

There is a growing consensus, based on several converging lines of evidence, which suggests schizophrenia is the product of a developmental insult occurring in the late 2 nd or early 3 rd trimester. Additionally, it has been observed that adults who abuse the noncompetitive NMDA antagonist PCP present with symptoms that mimic schizophrenia, such as hallucinations, formal thought disorder, delusions, unstable or flattened affect, social withdrawal, and impaired cognition. Thus, several labs have attempted to use early postnatal PCP administration in rodents as a drug model of schizophrenia. The current study investigated the cognitive effects of early postnatal PCP administration in C57BL/6 mice. Mouse pups received daily administrations of either 10.0 mg/kg PCP or saline on postnatal (PN) days 5-15. After weaning, pups were assessed in locomotor activity, a reference memory task in the Morris water maze, and a spatial delayed alternation task in the T-maze. Additionally, pups were subjected to a pharmacological challenge with PCP in the delayed alternation task. In males, No significant differences were detected between PCP- and saline-treated animals in locomotor activity. However, in the reference memory task, PCP-treated males had significantly longer path lengths, and displayed a non-significant trend towards increased thigmotaxia. Furthermore, males treated with PCP displayed significantly reduced accuracy in the working memory task without differences in choice latency, and were more sensitive to the acute effects of PCP than saline controls. Finally, these deficits were associated with a 29% increase in NR1 subunit expression in the hippocampus. Interestingly, PCP-treated female mice were not significantly different from saline-treated controls in locomotor activity, reference memory task performance, or delayed alternation performance, did not have a significantly different reaction to pharmacological challenge with PCP in the delayed alternation task, and did not demonstrate any changes in NR1 subunit expression. The present study provided the first evidence that early postnatal PCP administration in C57BL/6 mice can produce selective memory pairments. However, this effect was limited to the male mice, suggesting that the female mice were protected somewhat from these effects.

Name thesis:degree_name

Doctor of Philosophy

Level thesis:degree_level

Dissertation

Discipline thesis:degree_discipline

Psychology

Year dc:date.available

2007

Author dc:creator

• Pehrson, Alan L.

Contributors dc:contributor

• Dr. Joseph H. Porter

• Phencyclidine
• PCP
• Mouse
• Developmental
• Memory
• Schizophrenia
• Postnatal exposure
• Working memory
• Reference memory
• Locomotor
• Psychology
• Social and Behavioral Sciences

Statement dc:rights

• © The Author

Identifier

https://scholarscompass.vcu.edu/etd/878

OAI identifier oai:identifier

oai:scholarscompass.vcu.edu:etd-1877