The beta-lactam antibiotic, ceftriaxone, attenuates morphine-evoked hyperthermia in rats.
OBJECTIVE
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.


METHODS
A body temperature assay was used to determine if ceftriaxone decreased morphine-induced hyperthermia in rats by increasing glutamate uptake.


RESULTS
Body temperatures of rats treated with ceftriaxone (200 mg kg(-1), i.p. x 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 micromol, i.c.v.), an inhibitor of glutamate transport.


CONCLUSIONS
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.
Rawls
S M
SM
Department of Pharmaceutical Sciences, Temple University School of Pharmacy, Philadelphia, PA 19140, USA. scott.rawls@temple.edu
Tallarida
R
R
Robinson
W
W
Amin
M
M
D000701:Analgesics, Opioid / Q000008:administration & dosage / Q000633:toxicity; D000704:Analysis of Variance; D000818:Animals; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology; D001224:Aspartic Acid / Q000008:administration & dosage / Q000494:pharmacology; D001831:Body Temperature / Q000187:drug effects; D002443:Ceftriaxone / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D018691:Excitatory Amino Acid Antagonists / Q000008:administration & dosage / Q000494:pharmacology; D005334:Fever / Q000139:chemically induced / Q000378:metabolism / Q000517:prevention & control*; D018698:Glutamic Acid / Q000187:drug effects / Q000378:metabolism; D007274:Injections, Intraperitoneal; D007276:Injections, Intraventricular; D007279:Injections, Subcutaneous; D008297:Male; D009020:Morphine / Q000008:administration & dosage / Q000633:toxicity*; D051381:Rats; D017207:Rats, Sprague-Dawley; D019782:Riluzole / Q000494:pharmacology; D013997:Time Factors; D047090:beta-Lactams / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology
D000701:Analgesics, Opioid; D000900:Anti-Bacterial Agents; D018691:Excitatory Amino Acid Antagonists; C120673:benzyloxyaspartate; D047090:beta-Lactams; D001224:Aspartic Acid; D018698:Glutamic Acid; D002443:Ceftriaxone; D009020:Morphine; D019782:Riluzole