The beta‐lactam antibiotic, ceftriaxone, attenuates morphine‐evoked hyperthermia in rats

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Abstract
Background and purpose: Beta‐lactam antibiotics are the first practical pharmaceuticals capable of increasing the expression and activity of the glutamate transporter, GLT‐1, in the CNS. However, the functional impact of beta‐lactam antibiotics on specific drugs which produce their pharmacological effects by increasing glutamatergic transmission is unknown. One such drug is morphine, which causes hyperthermia in rats, mediated by an increase in glutamatergic transmission. Since drugs (e.g. antibiotics) that enhance glutamate uptake also decrease glutamatergic transmission, we tested the hypothesis that ceftriaxone, a beta‐lactam antibiotic, would block the glutamate‐dependent portion of morphine‐evoked hyperthermia.Experimental approach: A body temperature assay was used to determine if ceftriaxone decreased morphine‐induced hyperthermia in rats by increasing glutamate uptake.Key results: Body temperatures of rats treated with ceftriaxone (200 mg kg−1, i.p. × 7 days) did not differ from rats receiving saline. Morphine (1, 4, 8 and 15 mg kg−1, s.c.) caused significant hyperthermia. Pre‐treatment with ceftriaxone, as described above, decreased the hyperthermic response to these doses of morphine. The effects of ceftriaxone were prevented by TBOA (0.2 μmol, i.c.v.), an inhibitor of glutamate transport.Conclusions and implications: Ceftriaxone attenuated the hyperthermia caused by morphine, an effect prevented by inhibiting glutamate transport. Thus this effect of ceftriaxone was most likely mediated by increased glutamate uptake. These data revealed a functional interaction between ceftriaxone and morphine and indicated that a beta‐lactam antibiotic decreased the efficacy of morphine in conscious rats.British Journal of Pharmacology(2007)151, 1095–1102; doi:10.1038/sj.bjp.0707309