Effect of chronic administration of morphine on the gene expression level of sodium-dependent vitamin C transporters in rat hippocampus and lumbar spinal cord.
Chronic morphine leads to dependence, tolerance, and neural apoptosis. Vitamin C inhibits the withdrawal syndrome in morphine-dependent subjects and prevents apoptosis in experimental models. Sodium-dependent vitamin C transporter (SVCT) type-2 is the main transporter for carrying vitamin C into the brain and neural cells. The mechanism(s) by which vitamin C inhibits morphine dependence in not understood. SVCT activity determines the vitamin C availably within the nervous system. We have examined the alterations in the expression of SVCT1, SVCT2, and its splice variants in morphine-tolerant rats. Morphine (20 mg/kg) was injected twice/day to male rats for either 7 or 14 days. The development of analgesic tolerance was assessed using tail-flick test. Lumbar spinal cord and the hippocampus were isolated for RNA extraction. Semiquantitative reverse transcriptase-polymerase chain reaction method was used to assess the levels of gene expression. Administration of morphine for 7 or 14 days reduced the expression level of SVCT2 in both hippocampus and dorsal lumbar spinal cord of rats. SVCT2 expression was reduced in vitamin C-, and vitamin C combined with morphine-treated animals. Results did not show SVCT2 splice variation. SVCT1 did not express in control or morphine-treated rats. It seems that reduced expression level of SVCT2 might be involved in the development of morphine side effects such as tolerance and dependency.
Department of Physiology, School of Medical Sciences, Tarbiat Modares University, Tehran, Iran, P.O. Box: 14115-331. amirzarebkohan@yahoo.com
Amir
A
Zarebkohan
Mohammad
M
Javan
Leila
L
Satarian
Abolhasan
A
Ahmadiani
D000701:Analgesics, Opioid / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D004361:Drug Tolerance / Q000502:physiology; D015870:Gene Expression / Q000187:drug effects*; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D008159:Lumbar Vertebrae; D008297:Male; D009020:Morphine / Q000008:administration & dosage / Q000494:pharmacology*; D029363:Organic Anion Transporters, Sodium-Dependent / Q000235:genetics* / Q000378:metabolism; D010147:Pain Measurement; D051381:Rats; D017208:Rats, Wistar; D060347:Sodium-Coupled Vitamin C Transporters; D013116:Spinal Cord / Q000187:drug effects / Q000378:metabolism*; D027981:Symporters / Q000235:genetics* / Q000378:metabolism
D000701:Analgesics, Opioid; D029363:Organic Anion Transporters, Sodium-Dependent; C555162:SLC23A1 protein, human; C555163:SLC23A2 protein, human; C555166:Slc23a1 protein, rat; C555167:Slc23a2 protein, rat; D060347:Sodium-Coupled Vitamin C Transporters; D027981:Symporters; D009020:Morphine