title: Expression of spinal cord GABA transporter 1 in morphine-tolerant male Wistar rats.
abstract: Chronic morphine exposure produces morphine tolerance. One of the mechanisms of morphine tolerance involves γ-aminobutric acid (GABA), whose level is regulated by GABA transporter 1 (GAT-1). The aim of this study was to investigate the expression of GAT-1 in the spinal cord during morphine treatment. Morphine was administrated to rats via drinking water for 21 days. On day 21, a single dose of morphine (10mg/kg) was injected, followed by the administration of 5% formalin after 30 min. Expression of GAT-1 in the lumbar spinal cord during morphine treatment was analyzed by Western blotting and immunohistochemistry assay. In another set of experiments, a morphine-tolerant group was treated with a GAT-1 inhibitor, ethyl nipecotate (60 mg/kg), 5 min prior to the formalin test. To assess a possible analgesic effect of the GAT-1 inhibitor, a non-tolerant group was injected only with ethyl nipecotate 5 min prior to the formalin test. Our results indicated that a chronic consumption of morphine led to morphine tolerance. Morphine tolerance was also concomitant with GAT-1 up-regulation in the lumbar spinal cord. The GAT-1 inhibitor ethyl nipecotate improved the antinociceptive effect of morphine in the morphine-tolerant group. Ethyl nipecotate also had an antinociceptive effect on the non-tolerant group. Thus, our data suggest that GAT-1 overexpression in the spinal cord plays an important role in morphine tolerance.
authors.affiliation: Department of Physiology, Faculty of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
authors.forename: Siroosi
authors.initials: S
authors.lastname: Shokoofeh
authors.affiliation: Neurophysiology Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran. Electronic address: manahejih@sbmu.ac.ir.
authors.forename: Manaheji
authors.initials: M
authors.lastname: Homa
authors.affiliation: Neuroscience Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
authors.forename: Dargahi
authors.initials: D
authors.lastname: Leila
authors.affiliation: Neurophysiology Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
authors.forename: Daniali
authors.initials: D
authors.lastname: Samira
mesh_terms: D000700:Analgesics / Q000494:pharmacology; D000701:Analgesics, Opioid / Q000494:pharmacology; D000818:Animals; D004361:Drug Tolerance; D050485:GABA Plasma Membrane Transport Proteins / Q000096:biosynthesis*; D058805:GABA Uptake Inhibitors / Q000494:pharmacology; D008161:Lumbosacral Region; D008297:Male; D009020:Morphine / Q000494:pharmacology*; D009557:Nipecotic Acids / Q000494:pharmacology; D010147:Pain Measurement / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D013116:Spinal Cord / Q000187:drug effects / Q000378:metabolism*; D015854:Up-Regulation
chemical_list: D000700:Analgesics; D000701:Analgesics, Opioid; D050485:GABA Plasma Membrane Transport Proteins; D058805:GABA Uptake Inhibitors; D009557:Nipecotic Acids; C038002:nipecotic acid ethyl ester; D009020:Morphine
keywords: Ethyl nipecotate; Ethyl nipecotate (PubChem CID: 98969); Formalin test; GABA transporter 1 (GAT-1); Morphine; Morphine sulfate (PubChem CID: 5464280)