Abstract
Phencyclidine (PCP) induces a psychotic state that closely resembles schizophrenia. In preclinical studies, PCP has been shown to induce its unique behavioral effects by blocking excitatory neurotransmission mediated at the N-methyl-D-asparate (NMDA) receptors, suggesting that agents which potentiate NMDA receptor-mediated neurotransmission might have clinically beneficial effects. The present study demonstrates that the NMDA co-agonist glycine inhibits rodent hyperactivity induced by PCP, but not amphetamine. Glycyldodecylamide, a compound that blocks neuronal glycine uptake and which may therefore increase intrasynaptic glycine levels, inhibits PCP-induced hyperactivity more potently than glycine. These results complement recent clinical studies with glycine and suggest that glycine-uptake inhibitors, as well as glycine, may be beneficial in the treatment of PCP-induced psychosis and schizophrenia.
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Acknowledgements
This work was supported by NIDA research grant #R01 DA03383 and grants from the Theodore and Vada Stanley Foundation and Zara and Bernad Jakubovitz Fund for Brain Research to DCJ.
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Javitt, D., Sershen, H., Hashim, A. et al. Reversal of Phencyclidine-Induced Hyperactivity by Glycine and the Glycine Uptake Inhibitor Glycyldodecylamide. Neuropsychopharmacol 17, 202–204 (1997). https://doi.org/10.1016/S0893-133X(97)00047-X
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DOI: https://doi.org/10.1016/S0893-133X(97)00047-X
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