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dc.contributor.authorLeck, KJ
dc.contributor.authorBartlett, SE
dc.contributor.authorSmith, MT
dc.contributor.authorMegirian, D
dc.contributor.authorHolgate, J
dc.contributor.authorPowell, KL
dc.contributor.authorMatthaei, KI
dc.contributor.authorHendry, IA
dc.date.available2014-05-22T08:39:29Z
dc.date.available2003-11-21
dc.date.available2003-11-21
dc.date.available2003-11-21
dc.date.issued2004-05-01
dc.identifierpii: S0028390803004532
dc.identifier.citationLeck, K. J., Bartlett, S. E., Smith, M. T., Megirian, D., Holgate, J., Powell, K. L., Matthaei, K. I. & Hendry, I. A. (2004). Deletion of guanine nucleotide binding protein alpha(z) subunit in mice induces a gene dose dependent tolerance to morphine. NEUROPHARMACOLOGY, 46 (6), pp.836-846. https://doi.org/10.1016/j.neuropharm.2003.11.024.
dc.identifier.issn0028-3908
dc.identifier.urihttp://hdl.handle.net/11343/33307
dc.descriptionC1 - Journal Articles Refereed
dc.description.abstractThe mechanism underlying the development of tolerance to morphine is still incompletely understood. Morphine binds to opioid receptors, which in turn activates downstream second messenger cascades through heterotrimeric guanine nucleotide binding proteins (G proteins). In this paper, we show that G(z), a member of the inhibitory G protein family, plays an important role in mediating the analgesic and lethality effects of morphine after tolerance development. We blocked signaling through the G(z) second messenger cascade by genetic ablation of the alpha subunit of the G protein in mice. The Galpha(z) knockout mouse develops significantly increased tolerance to morphine, which depends on Galpha(z) gene dosage. Further experiments demonstrate that the enhanced morphine tolerance is not caused by pharmacokinetic and behavioural learning mechanisms. The results suggest that G(z) signaling pathways are involved in transducing the analgesic and lethality effects of morphine following chronic morphine treatment.
dc.formatapplication/pdf
dc.languageEnglish
dc.publisherPERGAMON-ELSEVIER SCIENCE LTD
dc.subjectCentral Nervous System; Nervous System and Disorders
dc.titleDeletion of guanine nucleotide binding protein alpha(z) subunit in mice induces a gene dose dependent tolerance to morphine
dc.typeJournal Article
dc.identifier.doi10.1016/j.neuropharm.2003.11.024
melbourne.peerreviewPeer Reviewed
melbourne.affiliationThe University of Melbourne
melbourne.affiliation.departmentMedicine - Royal Melbourne Hospital
melbourne.source.titleNeuropharmacology
melbourne.source.volume46
melbourne.source.issue6
melbourne.source.pages836-846
melbourne.publicationid139931
melbourne.elementsid542919
melbourne.contributor.authorPowell, Kim
dc.identifier.eissn1873-7064
melbourne.fieldofresearch320903 Central nervous system
melbourne.seocode200199 Clinical health not elsewhere classified
melbourne.accessrightsThis item is currently not available from this repository


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