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Effects of clozapine on memory function in the rat neonatal hippocampal lesion model of schizophrenia.

Publication ,  Journal Article
Levin, ED; Christopher, NC
Published in: Prog Neuropsychopharmacol Biol Psychiatry
March 2006

Clozapine is an effective atypical antipsychotic drug used to treat schizophrenia. It has the advantage of producing fewer extrapyramidal motor side effects than typical antipsychotic drugs such as haloperidol. Schizophrenia involves more than the hallmark symptom of psychosis. Substantial cognitive impairment is also seen. Effective drug treatments against the cognitive impairment of schizophrenia need to be developed. The current study was conducted to determine the effects of clozapine on working memory in the rat neonatal hippocampal lesion model of schizophrenia, which includes symptoms of cognitive impairment. Infant Sprague-Dawley rats were given ibotenic acid lesions of the hippocampus on day 7 of age (using the day of birth as day 0). Controls were given vehicle infusions. In adulthood, the rats were trained on the 8-arm radial maze using the win-shift procedure. After 6 sessions of training, the lesioned rats and their controls were administered repeated injections of saline or clozapine (2.5 mg/kg) for the next 12 sessions of training. The females had significant radial-arm maze choice accuracy impairments caused by either clozapine or the hippocampal lesion, but the combination of the two treatments had no additive effect. The males showed a different pattern of effects. Intact males did not show a significant clozapine-induced impairment, whereas males with hippocampal lesions did show significant clozapine-induced impairment although hippocampal lesions by themselves did not significantly impair male choice accuracy. These data show that clozapine can cause memory impairment and it potentiates rather than reverses hippocampal lesion-induced deficits. There are critical sex-related differences in these effects.

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Published In

Prog Neuropsychopharmacol Biol Psychiatry

DOI

ISSN

0278-5846

Publication Date

March 2006

Volume

30

Issue

2

Start / End Page

223 / 229

Location

England

Related Subject Headings

  • Sex Factors
  • Schizophrenia
  • Reaction Time
  • Rats, Sprague-Dawley
  • Rats
  • Random Allocation
  • Psychiatry
  • Pregnancy
  • Memory
  • Maze Learning
 

Citation

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ICMJE
MLA
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Levin, E. D., & Christopher, N. C. (2006). Effects of clozapine on memory function in the rat neonatal hippocampal lesion model of schizophrenia. Prog Neuropsychopharmacol Biol Psychiatry, 30(2), 223–229. https://doi.org/10.1016/j.pnpbp.2005.10.018
Levin, Edward D., and N Channelle Christopher. “Effects of clozapine on memory function in the rat neonatal hippocampal lesion model of schizophrenia.Prog Neuropsychopharmacol Biol Psychiatry 30, no. 2 (March 2006): 223–29. https://doi.org/10.1016/j.pnpbp.2005.10.018.
Levin ED, Christopher NC. Effects of clozapine on memory function in the rat neonatal hippocampal lesion model of schizophrenia. Prog Neuropsychopharmacol Biol Psychiatry. 2006 Mar;30(2):223–9.
Levin, Edward D., and N. Channelle Christopher. “Effects of clozapine on memory function in the rat neonatal hippocampal lesion model of schizophrenia.Prog Neuropsychopharmacol Biol Psychiatry, vol. 30, no. 2, Mar. 2006, pp. 223–29. Pubmed, doi:10.1016/j.pnpbp.2005.10.018.
Levin ED, Christopher NC. Effects of clozapine on memory function in the rat neonatal hippocampal lesion model of schizophrenia. Prog Neuropsychopharmacol Biol Psychiatry. 2006 Mar;30(2):223–229.
Journal cover image

Published In

Prog Neuropsychopharmacol Biol Psychiatry

DOI

ISSN

0278-5846

Publication Date

March 2006

Volume

30

Issue

2

Start / End Page

223 / 229

Location

England

Related Subject Headings

  • Sex Factors
  • Schizophrenia
  • Reaction Time
  • Rats, Sprague-Dawley
  • Rats
  • Random Allocation
  • Psychiatry
  • Pregnancy
  • Memory
  • Maze Learning