PMID- 17217924
OWN - NLM
STAT- MEDLINE
DCOM- 20080102
LR  - 20140325
IS  - 0006-3223 (Print)
IS  - 0006-3223 (Linking)
VI  - 62
IP  - 6
DP  - 2007 Sep 15
TI  - Tumor necrosis factor-alpha and its inducer inhibit morphine-induced rewarding 
      effects and sensitization.
PG  - 658-68
AB  - BACKGROUND: Tumor necrosis factor-alpha (TNF-alpha) is emerging as an important 
      modulator of the function of the central nervous system (CNS). We have 
      demonstrated that TNF-alpha or Leu-Ile, a TNF-alpha inducer, inhibits 
      methamphetamine-induced rewarding effects and sensitization. In this study, we 
      investigated the effects of TNF-alpha or Leu-Ile on morphine (MOR)-induced 
      rewarding effects and sensitization. METHODS: Levels of TNF-alpha messenger RNA 
      (mRNA) and protein were determined by real-time reverse transcription polymerase 
      chain reaction (RT-PCR) and immunohistochemistry. Effects of TNF-alpha or Leu-Ile 
      on MOR-induced rewarding effects and sensitization were investigated by 
      conditioned place preference and locomotor activity tests. Extracellular dopamine 
      levels were examined using in vivo microdialysis. Effects of TNF-alpha or Leu-Ile 
      on MOR-induced antinociceptive effect and withdrawal symptoms were examined by 
      hot plate test and naloxone-precipitated withdrawal. RESULTS: Morphine induced 
      TNF-alpha mRNA expression via dopamine and opioid receptors. Posttreatment with 
      TNF-alpha or Leu-Ile attenuated the MOR-induced place preference and 
      sensitization even after their development, as well as pretreatment with 
      TNF-alpha or Leu-Ile blocked them. An inhibitory effect of Leu-Ile on MOR-induced 
      place preference was not observed in TNF-alpha knockout mice. Tumor necrosis 
      factor-alpha or Leu-Ile inhibited the increase in extracellular dopamine levels 
      in the nucleus accumbens induced by repeated MOR treatment. CONCLUSIONS: These 
      results suggest that TNF-alpha inhibits MOR-induced rewarding effect and 
      sensitization by regulating extracellular dopamine levels, and Leu-Ile inhibits 
      them via the induction of TNF-alpha.
FAU - Niwa, Minae
AU  - Niwa M
AD  - Department of Neuropsychopharmacology and Hospital Pharmacy, Nagoya University 
      Graduate School of Medicine, 65 Tsuruma-cho, Showa-ku, Nagoya 466-8560, Japan.
FAU - Nitta, Atsumi
AU  - Nitta A
FAU - Yamada, Yuichiro
AU  - Yamada Y
FAU - Nakajima, Akira
AU  - Nakajima A
FAU - Saito, Kuniaki
AU  - Saito K
FAU - Seishima, Mitsuru
AU  - Seishima M
FAU - Noda, Yukihiro
AU  - Noda Y
FAU - Nabeshima, Toshitaka
AU  - Nabeshima T
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20070109
PL  - United States
TA  - Biol Psychiatry
JT  - Biological psychiatry
JID - 0213264
RN  - 0 (Dipeptides)
RN  - 0 (Narcotic Antagonists)
RN  - 0 (Narcotics)
RN  - 0 (RNA, Messenger)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 0 (leucyl-isoleucyl)
RN  - 36B82AMQ7N (Naloxone)
RN  - 76I7G6D29C (Morphine)
SB  - IM
EIN - Biol Psychiatry. 2011 Mar 15;69(6):608
MH  - Animals
MH  - Behavior, Animal/drug effects
MH  - Conditioning, Operant/drug effects
MH  - Dipeptides/*pharmacology/therapeutic use
MH  - Habituation, Psychophysiologic/*drug effects
MH  - Male
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Morphine/*antagonists & inhibitors/pharmacology
MH  - Morphine Dependence/drug therapy/*psychology
MH  - Motor Activity/drug effects
MH  - Naloxone/pharmacology
MH  - Narcotic Antagonists/pharmacology
MH  - Narcotics/pharmacology
MH  - RNA, Messenger/metabolism
MH  - *Reward
MH  - Spatial Behavior/drug effects
MH  - Substance Withdrawal Syndrome/etiology
MH  - Tumor Necrosis Factor-alpha/*pharmacology/therapeutic use
EDAT- 2007/01/16 09:00
MHDA- 2008/01/03 09:00
CRDT- 2007/01/16 09:00
PHST- 2006/05/23 00:00 [received]
PHST- 2006/09/30 00:00 [revised]
PHST- 2006/10/04 00:00 [accepted]
PHST- 2007/01/16 09:00 [pubmed]
PHST- 2008/01/03 09:00 [medline]
PHST- 2007/01/16 09:00 [entrez]
AID - S0006-3223(06)01267-4 [pii]
AID - 10.1016/j.biopsych.2006.10.009 [doi]
PST - ppublish
SO  - Biol Psychiatry. 2007 Sep 15;62(6):658-68. doi: 10.1016/j.biopsych.2006.10.009. 
      Epub 2007 Jan 9.