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      Beta-lactam antibiotic reduces morphine analgesic tolerance in rats through GLT-1 transporter activation

      , , , , ,
      Drug and Alcohol Dependence
      Elsevier BV

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          Abstract

          Glutamate transporter subtype 1 (GLT-1) activation is a promising - and understudied - approach for managing aspects of morphine tolerance caused by increased glutamatergic transmission. Identification of beta-lactam antibiotics as pharmaceuticals which activate GLT-1 transporters prompted us to hypothesize that repeated beta-lactam antibiotic (ceftriaxone) administration blocks development of tolerance to morphine antinociception through GLT-1 activation. Here, we injected rats with morphine (10mg/kg, s.c.) twice daily for 7 days to induce tolerance and used the hot-plate assay to determine antinociception on days 1, 4 and 7 of repeated morphine administration. Ceftriaxone and a selective GLT-1 transporter inhibitor dihydrokainate (DHK) were co-administered with morphine to determine if GLT-1 activation mediated the ceftriaxone effect. Tolerance was present on days 4 and 7 of repeated morphine administration. Ceftriaxone (50, 100 or 200mg/kg, i.p.) administration dose-dependently blocked development of morphine tolerance. DHK (10mg/kg, s.c.), administered 15 min before each morphine injection, prevented inhibition of morphine tolerance by ceftriaxone (200mg/kg, i.p.). These results identify an interaction between ceftriaxone and morphine in opioid-tolerant rats and suggest beta-lactam antibiotics preserve analgesic efficacy during chronic morphine exposure. Copyright 2009 Elsevier Ireland Ltd. All rights reserved.

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          Author and article information

          Journal
          Drug and Alcohol Dependence
          Drug and Alcohol Dependence
          Elsevier BV
          03768716
          March 01 2010
          March 01 2010
          : 107
          : 2-3
          : 261-263
          Article
          10.1016/j.drugalcdep.2009.10.010
          2921944
          20004063
          52ea17f1-4219-4da4-a1c8-8e56802b09fc
          © 2010

          https://www.elsevier.com/tdm/userlicense/1.0/

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