PMID- 18400403
OWN - NLM
STAT- MEDLINE
DCOM- 20090608
LR  - 20131121
IS  - 1873-7544 (Electronic)
IS  - 0306-4522 (Linking)
VI  - 153
IP  - 3
DP  - 2008 May 15
TI  - Amitriptyline induces nuclear transcription factor-kappaB-dependent glutamate 
      transporter upregulation in chronic morphine-infused rats.
PG  - 823-31
LID - 10.1016/j.neuroscience.2008.02.055 [doi]
AB  - We previously showed that intrathecal co-administration of amitriptyline with 
      morphine upregulates the expression of the glial glutamate transporters 
      glutamate-aspartate transporter (GLAST) and glutamate transporter-1 (GLT-1) and 
      restores neuronal glutamate transporter excitatory amino acid carrier 1 (EAAC1) 
      expression in chronically morphine-infused rats. The present study examined the 
      role of nuclear transcription factor-kappaB (NF-kappaB) in the regulation of the 
      expression of GLAST, GLT-1, and EAAC1 following long-term amitriptyline/morphine 
      co-infusion. Male Wistar rats were implanted with two intrathecal catheters with 
      or without a microdialysis probe; one of the catheters was used for continuous 
      infusion of saline (control), morphine (15 microg/h), or morphine plus 
      amitriptyline (both 15 microg/h) for 5 days, while the other was used for a 
      single daily intrathecal injection of the NF-kappaB inhibitor Ro106-9920 (10 
      microl of 10 microM) for 5 days. We found that amitriptyline co-infusion restored 
      the antinociceptive effect of morphine (4.5-fold right-shift in the morphine 
      dose-response curve compared with a 65-fold right-shift in its absence) and this 
      effect was inhibited by Ro106-9920 administration (48-fold right-shift). 
      Moreover, amitriptyline/morphine co-infusion increased IkappaBalpha 
      phosphorylation and the translocation of NF-kappaB p65 from the cytosol to the 
      nucleus. Daily intrathecal injection of Ro106-9920 prevented the 
      amitriptyline/morphine-induced NF-kappaB p65 translocation and reversed the 
      amitriptyline/morphine-induced GLAST and GLT-1 upregulation and inhibited the 
      restoration of EAAC1 expression. The Ro106-9920 injections abolished the 
      inhibitory effect of amitriptyline on the morphine-evoked release of excitatory 
      amino acids into the spinal cerebrospinal fluid (CSF) dialysates. In conclusion, 
      amitriptyline/morphine co-infusion restores the antinociceptive effect of 
      morphine and upregulates GLAST and GLT-1 expression and restores EAAC1 expression 
      to baseline levels, thus reducing excitatory amino acid levels in the spinal CSF 
      dialysates. The mechanism involves activation of the NF-kappaB pathway, but may 
      also involve other pathways.
FAU - Tai, Y-H
AU  - Tai YH
AD  - Department of Anesthesiology, Tri-service General Hospital and National Defense 
      Medical Center, Taipei, Taiwan.
FAU - Tsai, R-Y
AU  - Tsai RY
FAU - Wang, Y-H
AU  - Wang YH
FAU - Cherng, C-H
AU  - Cherng CH
FAU - Tao, P-L
AU  - Tao PL
FAU - Liu, T-M
AU  - Liu TM
FAU - Wong, C-S
AU  - Wong CS
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20080306
PL  - United States
TA  - Neuroscience
JT  - Neuroscience
JID - 7605074
RN  - 0 (Adrenergic Uptake Inhibitors)
RN  - 0 (Amino Acid Transport System X-AG)
RN  - 0 (Excitatory Amino Acids)
RN  - 0 (NF-kappa B)
RN  - 0 (Narcotics)
RN  - 0 (Ro 106-9920)
RN  - 0 (Sulfoxides)
RN  - 0 (Tetrazoles)
RN  - 1806D8D52K (Amitriptyline)
RN  - 76I7G6D29C (Morphine)
SB  - IM
MH  - Adrenergic Uptake Inhibitors/*administration & dosage
MH  - Amino Acid Transport System X-AG/*drug effects/metabolism
MH  - Amitriptyline/*administration & dosage
MH  - Animals
MH  - Blotting, Western
MH  - Dose-Response Relationship, Drug
MH  - Drug Interactions
MH  - Drug Tolerance/physiology
MH  - Excitatory Amino Acids/metabolism
MH  - Fluorescent Antibody Technique
MH  - Gene Expression Regulation/drug effects
MH  - Image Processing, Computer-Assisted
MH  - Injections, Spinal
MH  - Male
MH  - Microdialysis
MH  - Morphine/pharmacology
MH  - NF-kappa B/*drug effects/metabolism
MH  - Narcotics/*pharmacology
MH  - Pain Threshold/drug effects
MH  - Rats
MH  - Rats, Wistar
MH  - Sulfoxides/pharmacology
MH  - Tetrazoles/pharmacology
MH  - Up-Regulation
EDAT- 2008/04/11 09:00
MHDA- 2009/06/09 09:00
CRDT- 2008/04/11 09:00
PHST- 2007/11/15 00:00 [received]
PHST- 2008/02/11 00:00 [revised]
PHST- 2008/02/18 00:00 [accepted]
PHST- 2008/04/11 09:00 [pubmed]
PHST- 2009/06/09 09:00 [medline]
PHST- 2008/04/11 09:00 [entrez]
AID - S0306-4522(08)00301-1 [pii]
AID - 10.1016/j.neuroscience.2008.02.055 [doi]
PST - ppublish
SO  - Neuroscience. 2008 May 15;153(3):823-31. doi: 10.1016/j.neuroscience.2008.02.055. 
      Epub 2008 Mar 6.