Role of the guanine nucleotide binding protein, Gα in the development of morphine tolerance and dependence.
Rationale: The use of morphine and other opioids for chronic pain is limited by the development of analgesic tolerance and physical dependence. Morphine produces its effects by activating the μ opioid receptor, which couples to Gα-containing heterotrimeric G proteins. Evidence suggests that the anti...
| Publicado en: | Psychopharmacology Vol. 235; no. 1; pp. 71 - 83 |
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| Autores principales: | , , , |
| Formato: | Journal Article |
| Publicado: |
Springer Nature
Jan2018
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| Acceso en línea: | Ver este registro en EBSCOhost |
| fields | @attributes: recordID: 1 pdfLink: plink: https://search.ebscohost.com/login.aspx?direct=true&db=ccm&AN=127041139&site=ehost-live header: @attributes: shortDbName: ccm uiTerm: 127041139 longDbName: CINAHL Complete uiTag: AN controlInfo: bkinfo: dissinfo: jinfo: jid: 00333158 EJD jtl: Psychopharmacology issn: 00333158 maglogo: N pubinfo: dt: Jan2018 vid: 235 iid: 1 pid: 237 pub: Springer Nature place: New York, New York artinfo: ui: 127041139 10.1007/s00213-017-4742-2 127041139 ppf: 71 ppct: 12 formats: fmt: – @attributes: type: T – @attributes: type: P tig: atl: Role of the guanine nucleotide binding protein, Gα in the development of morphine tolerance and dependence. aug: au: Lamberts, Jennifer T. Rosenthal, Lisa D. Jutkiewicz, Emily M. Traynor, John R. affil: Department of Pharmacology and Edward F. Domino Research Center, University of Michigan Medical School, 1150 W. Medical Center Dr., 1301 MSRB III, 48109-5632, Ann Arbor, MI, USA sug: ab: Rationale: The use of morphine and other opioids for chronic pain is limited by the development of analgesic tolerance and physical dependence. Morphine produces its effects by activating the μ opioid receptor, which couples to Gα-containing heterotrimeric G proteins. Evidence suggests that the antinociceptive effects of morphine are mediated by Gα. However, the role of Gα in the development of morphine tolerance and dependence is unknown . Objective: The objective of the study is to evaluate the contribution of Gα to the development of morphine tolerance and dependence in mice. Methods: 129S6 mice lacking one copy of the Gα gene (Gα +/−) were administered morphine acutely or chronically. Mice were examined for tolerance to the antinociceptive action of morphine using the 52 °C hot plate as the nociceptive stimulus and for dependence by evaluating the severity of naltrexone-precipitated withdrawal. Wild-type littermates of the Gα +/− mice were used as controls. Changes in μ receptor number and function were determined in midbrain and hindbrain homogenates using radioligand binding and μ agonist-stimulated [S]GTPγS binding, respectively. Results: Following either acute or chronic morphine treatment, all mice developed antinociceptive tolerance and physical dependence, regardless of genotype. With chronic morphine treatment, Gα +/− mice developed tolerance faster and displayed more severe naltrexone-precipitated withdrawal in some behaviors than did wild-type littermates. Morphine tolerance was not associated with changes in μ receptor number or function in brain homogenates from either wild-type or Gα +/− mice. Conclusions: These data suggest that the guanine nucleotide binding protein Gα offers some protection against the development of morphine tolerance and dependence. pubtype: Academic Journal doctype: Journal Article ougenre: Article language: English refInfo: holdings: @attributes: islocal: N |
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