Postnatal analgesic effects of racemic methadone and its isomers in 129/SvEv and CD-1 mouse pups.
Item
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Title
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Postnatal analgesic effects of racemic methadone and its isomers in 129/SvEv and CD-1 mouse pups.
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Identifier
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AAI3159197
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identifier
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3159197
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Creator
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Baliram, Ramkumarie.
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Contributor
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Adviser: Gordon A. Barr
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Date
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2005
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Language
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English
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Publisher
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City University of New York.
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Subject
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Psychology, Psychobiology | Biology, Neuroscience
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Abstract
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Experiment one. The postnatal analgesic effects of racemic methadone and its isomers in the 129/SvEv and CD-1 mouse pups in the formalin test were studied. The CD-1 pups were used as a control as the 129/SvEv mouse has been reported to have putative deficits of the mu-opioid or NMDA receptors. Fifteen minutes post drug injection pups were injected with dilute formalin and behavioral responses were observed for 45 minutes. dl-Methadone and its enantiomers resulted in greater analgesic effectiveness at, PD 3 and 10 than at PD 21. Also, l- and dl-methadone were effective analgesics, in both phases of the formalin test and d-methadone was only minimally effective in the second phase.;Experiment two. The postnatal analgesic effects of racemic methadone and its isomers in the 129/SvEv and the CD-1 mouse pups in the thermal test were studied. Pups were injected with either vehicle or each of four doses of either: d-, l- or dl-methadone in a cumulative dose response paradigm. Thirty minutes post-drug injection, appendage withdrawal latencies were taken as indicators of nociception. Results showed that all drugs were more effective at PD 3 than at PD 21. dl-Methadone exerted potentiated analgesia at the younger ages tested but not at PD 21, suggesting an interaction of the mu-opioid and the NMDA receptors. The analgesic effects exerted by dl-methadone at PD 21, are consistent with those of adults where 1-methadone was more effective than dl-methadone and d-methadone was the least effective drug tested.;Experiment three. Morphine and MK801 were co-administered to mimic the potentiated effects of dl-methadone at PD 3 and 10. MK801 did not potentiate the analgesic effects of morphine in both mouse strains, suggesting the mu-opioid and the NMDA receptors were not interacting in dl-methadone potentiated analgesia. There was no evidence that the NMDA receptor was playing a role in the potentiated analgesic effects of dl-methadone and d-methadone, as MK801 was not an effective analgesic. d-Methadone likely exerted minimal analgesic effects in phasic and tonic nociception at other receptors, other than the NMDA receptors.
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Type
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dissertation
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Source
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PQT Legacy CUNY.xlsx
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degree
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Ph.D.
