title: [Participation of glucocorticoid receptors in morphine tolerance development through the signal pathway of extracellular signal-regulated kinase].
abstract: OBJECTIVE
  To investigate the mechanism of glucocorticoid receptors (GR) participating in morphine tolerance development via the extracellular signal-regulated kinase (ERK) signal pathway.
  
  
  METHODS
  Forty healthy male SD rats were implanted with intrathecal catheters and then randomized into 4 groups: Group C received an intrathecal injection of 10 µl saline, Group M 10 µg morphine, Group MR 10 µg morphine followed by 2 µg GR antagonist RU38486 and Group MD 10 µg morphine followed by 4 µg GR agonist dexamethasone (DEX) respectively. Each intrathecal drug was administered twice daily for 7 days. Tail-flick test was employed to evaluate the thermal hyperalgesia. After tail-flick test at Day 8, the lumbar intamescentias were isolated by Western blot to examine the protein expressions of Mu opioid receptor (MOR), GR and pERK. And terminal deoxynucleotidyl transferase mediated X-dUTP nick end labeling (TUNEL) stain was performed.
  
  
  RESULTS
  DEX and RU38486 enhanced and inhibited morphine induced hyperalgesia to heat respectively. Compared with Group M (count of spinal dorsal horn apoptotic cells 5.4 ± 1.1, protein expression: MOR 37 ± 5, GR 20 ± 6, pERK(1) 39 ± 4, pERK(2) 41 ± 5), apoptotic cells decreased in Group MR (3.2 ± 0.4) (P < 0.01) and increased in Group MD (16.0 ± 1.6) (P < 0.01); the protein expressions of MOR (28 ± 5), GR (12 ± 6), pERK(1)(33 ± 4) and pERK(2)(34 ± 5) were down-regulated in Group MR (P < 0.01) while up-regulated in Group MD (55 ± 6, 28 ± 9, 49 ± 6, 59 ± 5) (P < 0.01).
  
  
  CONCLUSIONS
  The activity of glucocorticoid receptors affects the morphine-induced spinal neural apoptosis and the expression of spinal pERK in morphine tolerance.
authors.affiliation: Department of Anesthesiology, General Hospital of Tianjin Medical University, Tianjin 300052, China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Chen
authors.forename: Yong-Hao
authors.initials: YH
authors.lastname: Yu
authors.forename: Mei-Li
authors.initials: ML
authors.lastname: Zhai
authors.forename: Zhuang
authors.initials: Z
authors.lastname: Wang
authors.forename: Guo-Lin
authors.initials: GL
authors.lastname: Wang
mesh_terms: D000818:Animals; D004361:Drug Tolerance; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism*; D008297:Male; D009020:Morphine / Q000378:metabolism / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011965:Receptors, Glucocorticoid / Q000378:metabolism*; D015398:Signal Transduction
chemical_list: D011965:Receptors, Glucocorticoid; D009020:Morphine; D048049:Extracellular Signal-Regulated MAP Kinases