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Role of GLT-1 transporter activation in prevention of cannabinoid tolerance by the β-lactam antibiotic, ceftriaxone, in mice.

Abstract

Recently, it has been indicated that beta lactam antibiotics offer neuroprotection by increasing glutamate transporter expression. Furthermore, these antibiotics have been shown to prevent the development of tolerance and dependence to opioids. Since cannabinoid tolerance is known to be similar to opioids, our purpose was to examine the effect of ceftriaxone on the development of tolerance to WIN 55,212-2, a cannabinoid agonist. The tail flick test, a rectal thermometer, and the ring test were used for evaluating the degree of tolerance to the analgesic, hypothermic, and cataleptic effects of WIN 55,212-2, respectively. Within one week, animals became completely tolerant to analgesic, hypothermic and cataleptic effects of WIN 55,212-2 (6mg/kg). Ceftriaxone, with its higher doses (100-200mg/kg), attenuated the development of tolerance to the analgesic and hypothermic effects of WIN 55,212-2, but had no effect on its cataleptic action. Dihydrokainic acid (10mg/kg), a GLT-1 transporter inhibitor, prevented this effect of ceftriaxone. Our results suggest that repeated treatment with ceftriaxone prevents the development of tolerance to the analgesic and hypothermic effects of cannabinoids, and GLT-1 activation appears to play a key role in this preventive effect of beta-lactam antibiotics.

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  • Authors+Show Affiliations

    ,

    Department of Pharmacology, Faculty of Medicine, Trakya University, 22030-Edirne, Turkey.

    ,

    Source

    MeSH

    Animals
    Anti-Bacterial Agents
    Cannabinoids
    Ceftriaxone
    Drug Tolerance
    Excitatory Amino Acid Transporter 2
    Male
    Mice
    Mice, Inbred BALB C
    Pain Measurement
    beta-Lactams

    Pub Type(s)

    Comparative Study
    Journal Article

    Language

    eng

    PubMed ID

    21536061

    Citation

    * When formatting your citation, note that all book, journal, and database titles should be italicized* Article titles in AMA citation format should be in sentence-case
    TY - JOUR T1 - Role of GLT-1 transporter activation in prevention of cannabinoid tolerance by the β-lactam antibiotic, ceftriaxone, in mice. AU - Gunduz,Ozgur, AU - Oltulu,Cagatay, AU - Ulugol,Ahmet, Y1 - 2011/04/21/ PY - 2010/12/21/received PY - 2011/03/11/revised PY - 2011/04/15/accepted PY - 2011/5/4/entrez PY - 2011/5/4/pubmed PY - 2012/4/3/medline SP - 100 EP - 3 JF - Pharmacology, biochemistry, and behavior JO - Pharmacol. Biochem. Behav. VL - 99 IS - 1 N2 - Recently, it has been indicated that beta lactam antibiotics offer neuroprotection by increasing glutamate transporter expression. Furthermore, these antibiotics have been shown to prevent the development of tolerance and dependence to opioids. Since cannabinoid tolerance is known to be similar to opioids, our purpose was to examine the effect of ceftriaxone on the development of tolerance to WIN 55,212-2, a cannabinoid agonist. The tail flick test, a rectal thermometer, and the ring test were used for evaluating the degree of tolerance to the analgesic, hypothermic, and cataleptic effects of WIN 55,212-2, respectively. Within one week, animals became completely tolerant to analgesic, hypothermic and cataleptic effects of WIN 55,212-2 (6mg/kg). Ceftriaxone, with its higher doses (100-200mg/kg), attenuated the development of tolerance to the analgesic and hypothermic effects of WIN 55,212-2, but had no effect on its cataleptic action. Dihydrokainic acid (10mg/kg), a GLT-1 transporter inhibitor, prevented this effect of ceftriaxone. Our results suggest that repeated treatment with ceftriaxone prevents the development of tolerance to the analgesic and hypothermic effects of cannabinoids, and GLT-1 activation appears to play a key role in this preventive effect of beta-lactam antibiotics. SN - 1873-5177 UR - https://www.unboundmedicine.com/medline/citation/21536061/abstract/Role_of_GLT_1_transporter_activation_in_prevention_of_cannabinoid_tolerance_by_the_beta_lactam_antibiotic_ceftriaxone_in_mice_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0091-3057(11)00122-5 DB - PRIME DP - Unbound Medicine ER -