Risperidone Pretreatment Prevents Elevated Locomotor Activity Following Neonatal Hippocampal Lesions
Open accessAbstract
Long-standing behavioral abnormalities emerge after puberty in rats following neonatal hippocampal lesion, providing a developmental model of abnormal rat behavior that may have predictive validity in identifying compounds effective in treating symptoms of schizophrenia. We sought to test the predictive validity of the neonatal hippocampal lesion model in identifying preventive treatment for first-episode psychosis. We determined the effect of risperidone, recently studied for prevention of first-episode psychosis, on the development of elevated locomotor activity following neonatal hippocampal lesions. Rat pups received hippocampal or sham lesions on postnatal day 7, followed by treatment with risperidone or vehicle from postnatal days 35 to 56. Locomotor activity in response to novelty, amphetamine, and nocturnal locomotion were determined on postnatal day 57. Low-dose risperidone (45 microg/kg) pretreatment prevented elevated locomotor activity in some, but not all, of the behavioral tasks following neonatal hippocampal lesions. In contrast, higher risperidone pretreatment was less effective in preventing elevated locomotor activity following neonatal hippocampal lesions. Because low risperidone dosages were also found to be effective in preventing first-episode psychosis in human studies, these data support the predictive validity of the hippocampal lesion model in identifying medications for prevention of first-episode psychosis. Additionally, these data support the use of low-dose risperidone in psychosis prevention, and suggest the possibility that higher risperidone doses could be less effective in this application.
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Administration of antipsychotics during adolescence diminishes schizophrenia-like phenotypes in adults in the NVHL model.
“This idea is supported by studies in the NVHL model for schizophrenia, in which administration of antipsychotics during adolescence diminishes schizophrenia-like phenotypes in adults 62 .”
From Developmental timing and critical windows for the treatment of psychiatric disorders (2016) · cites this paper as [62]
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- Authors
- Richtand, N. M., Taylor, B., Welge, J. A., Ahlbrand, R., Ostrander, M. M., Burr, J., Hayes, S., Coolen, L. M., Pritchard, L. M., Logue, A., Herman, J. P., & McNamara, R. K.
- Affiliations
- Cincinnati VA Medical Center (US)
- University of Cincinnati (US)
- Corresponding author
- Richtand, Neil M
- Venue
- Neuropsychopharmacology
- Published
- 2005-06-15
- Volume
- 31
- Issue
- 1
- Pages
- 77-89
- ISSN
- 0893-133X (ISSN-L)
- 1740-634X
- PMC
- PMC1847785
- OpenAlex
- W2051643962
- Cited by
- 45
- References
- 5
- Citations by year
- 2022: 2 · 2021: 1 · 2020: 2 · 2016: 5 · 2015: 3 · 2014: 3 · 2013: 5 · 2012: 5
- FWCI
- 1.01
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Neuropsychopharmacology (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- U.S. Department of Veterans Affairs
- National Institute on Drug Abuse (DA 016778-01, R01DA016778)
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Schizophrenia research and treatment
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Life Sciences › Neuroscience › Biological Psychiatry › Tryptophan and brain disorders
- Keywords
- risperidone, predictive validity, schizophrenia, amphetamine response, novelty-induced locomotion, low-dose antipsychotics
- MeSH terms
- Amphetamine, Animals, Animals, Newborn, Circadian Rhythm, Female, Hippocampus, Ibotenic Acid, Motor Activity, Pregnancy, Antipsychotic Agents, Rats, Sprague-Dawley, Excitatory Amino Acid Agonists, Dopamine Uptake Inhibitors, Dentate Gyrus, Risperidone, Rats
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