beta-Lactam antibiotic inhibits development of morphine physical dependence in rats.
beta-Lactam antibiotics enhance cellular glutamate uptake. As increased glutamatergic transmission is a primary mediator of opiate dependence, we tested the hypothesis that a beta-lactam antibiotic (ceftriaxone) prevents development of morphine physical dependence in rats. Morphine (20 mg/kg) was injected twice daily for 10 days to induce physical dependence. Naloxone (10 mg/kg) administration 1, 48, and 96 h after the last morphine injection induced a withdrawal syndrome characterized by the appearance of wet-dog shakes, teeth chattering, eye blinking, jumping, and paw tremor. Ceftriaxone (150, 200 mg/kg) injected once daily during chronic morphine exposure inhibited each naloxone-precipitated withdrawal sign. Ceftriaxone efficacy persisted even after the 96 h-naloxone (10 mg/kg) injection. These results suggest that beta-lactam antibiotics inhibit processes leading to development of morphine physical dependence.
Rawls
Scott M
SM
Department of Pharmaceutical Sciences, Temple University Health Sciences Center, Philadelphia, Pennsylvania 1914, USA. scott.rawls@temple.edu
Baron
David A
DA
Kim
Jae
J
D000818:Animals; D000900:Anti-Bacterial Agents / Q000627:therapeutic use*; D002443:Ceftriaxone / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D008297:Male; D009020:Morphine / Q000037:antagonists & inhibitors / Q000494:pharmacology; D009021:Morphine Dependence / Q000517:prevention & control*; D009270:Naloxone / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000494:pharmacology; D009294:Narcotics / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013375:Substance Withdrawal Syndrome / Q000517:prevention & control*; D013997:Time Factors
D000900:Anti-Bacterial Agents; D009292:Narcotic Antagonists; D009294:Narcotics; D009270:Naloxone; D002443:Ceftriaxone; D009020:Morphine