Effect of ceftriaxone and topiramate treatments on naltrexone-precipitated morphine withdrawal and glutamate receptor desensitization in the rat locus coeruleus
Abstract
Morphine withdrawal is associated with a hyperactivity of locus coeruleus (LC) neurons by an elevated glutamate neurotransmission in this nucleus. We postulate that reductions in the amount of glutamate in the LC by enhancing its reuptake or inhibiting its release could attenuate the behavioral and cellular consequences of morphine withdrawal. We investigated the effect of chronic treatment with ceftriaxone (CFT), an excitatory amino acid transporter (EAAT2) enhancer, and acute administration of topiramate (TPM), a glutamate release inhibitor, on morphine withdrawal syndrome and withdrawal-induced glutamate receptor (GluR) desensitization in LC neurons from morphine-dependent rats. Morphine withdrawal behavior was measured after naltrexone administration in rats implanted with a morphine (200 mg kg(-1)) emulsion for 3 days. GluR desensitization in the LC was assessed by performing concentration-effect curves for glutamate by extracellular electrophysiological recordings in vitro. Treatments with CFT or TPM reduced, in a dose-related manner, the total behavioral score of naltrexone-precipitated morphine withdrawal. CFT and TPM, at doses that were effective in behavioral tests, also reduced the induction of GluR desensitization n...Continue Reading
References
Transporters for L-glutamate: an update on their molecular pharmacology and pathological involvement
Citations
Nephroprotective efficacy of ceftriaxone against cisplatin-induced subchronic renal fibrosis in rats
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