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.