Rawls Scott M, Baron David A, Kim Jae
Department of Pharmaceutical Sciences, Temple University Health Sciences Center, Philadelphia, Pennsylvania 1914, USA.
Behav Pharmacol. 2010 Mar;21(2):161-4. doi: 10.1097/FBP.0b013e328337be10.
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.
β-内酰胺类抗生素可增强细胞对谷氨酸的摄取。由于谷氨酸能传递增加是阿片类药物依赖的主要介导因素，我们检验了以下假设：β-内酰胺类抗生素（头孢曲松）可预防大鼠吗啡身体依赖性的形成。每天两次注射吗啡（20mg/kg），持续10天以诱导身体依赖性。在最后一次注射吗啡后1、48和96小时给予纳洛酮（10mg/kg），诱发戒断综合征，其特征为出现湿狗样抖动、牙齿打颤、眨眼、跳跃和爪部震颤。在慢性吗啡暴露期间每天注射一次头孢曲松（150、200mg/kg）可抑制每种纳洛酮诱发的戒断症状。即使在注射96小时的纳洛酮（10mg/kg）后，头孢曲松的疗效仍然持续。这些结果表明，β-内酰胺类抗生素可抑制导致吗啡身体依赖性形成的过程。
