Tumor Necrosis Factor-α and Its Inducer Inhibit Morphine-Induced Rewarding Effects and Sensitization

Minae Niwa, Atsumi Nitta, Yuichiro Yamada, Akira Nakajima, Kuniaki Saito, Mitsuru Seishima, Yukihiro Noda, Toshitaka Nabeshima

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32 Citations (Scopus)

Abstract

Background: Tumor necrosis factor-α (TNF-α) is emerging as an important modulator of the function of the central nervous system (CNS). We have demonstrated that TNF-α or Leu-Ile, a TNF-α inducer, inhibits methamphetamine-induced rewarding effects and sensitization. In this study, we investigated the effects of TNF-α or Leu-Ile on morphine (MOR)-induced rewarding effects and sensitization. Methods: Levels of TNF-α messenger RNA (mRNA) and protein were determined by real-time reverse transcription polymerase chain reaction (RT-PCR) and immunohistochemistry. Effects of TNF-α 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-α or Leu-Ile on MOR-induced antinociceptive effect and withdrawal symptoms were examined by hot plate test and naloxone-preciptated withdrawal. Results: Morphine induced TNF-α mRNA expression via dopamine and opioid receptors. Posttreatment with TNF-α or Leu-Ile attenuated the MOR-induced place preference and sensitization even after their development, as well as pretreatment with TNF-α or Leu-Ile blocked them. An inhibitory effect of Leu-Ile on MOR-induced place preference was not observed in TNF-α knockout mice. Tumor necrosis factor-α 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-α inhibits MOR-induced rewarding effect and sensitization by regulating extracellular dopamine levels, and Leu-Ile inhibits them via the induction of TNF-α.

Original languageEnglish
Pages (from-to)658-668
Number of pages11
JournalBiological Psychiatry
Volume62
Issue number6
DOIs
Publication statusPublished - 15-09-2007

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Morphine
Tumor Necrosis Factor-alpha
Dopamine
Substance Withdrawal Syndrome
Messenger RNA
Methamphetamine
Microdialysis
Dopamine Receptors
Nucleus Accumbens
Opioid Receptors
Locomotion
Naloxone
Knockout Mice
Reverse Transcription
Central Nervous System
Immunohistochemistry

All Science Journal Classification (ASJC) codes

  • Biological Psychiatry

Cite this

Niwa, Minae ; Nitta, Atsumi ; Yamada, Yuichiro ; Nakajima, Akira ; Saito, Kuniaki ; Seishima, Mitsuru ; Noda, Yukihiro ; Nabeshima, Toshitaka. / Tumor Necrosis Factor-α and Its Inducer Inhibit Morphine-Induced Rewarding Effects and Sensitization. In: Biological Psychiatry. 2007 ; Vol. 62, No. 6. pp. 658-668.
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Tumor Necrosis Factor-α and Its Inducer Inhibit Morphine-Induced Rewarding Effects and Sensitization. / Niwa, Minae; Nitta, Atsumi; Yamada, Yuichiro; Nakajima, Akira; Saito, Kuniaki; Seishima, Mitsuru; Noda, Yukihiro; Nabeshima, Toshitaka.

In: Biological Psychiatry, Vol. 62, No. 6, 15.09.2007, p. 658-668.

Research output: Contribution to journalArticle

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AU - Niwa, Minae

AU - Nitta, Atsumi

AU - Yamada, Yuichiro

AU - Nakajima, Akira

AU - Saito, Kuniaki

AU - Seishima, Mitsuru

AU - Noda, Yukihiro

AU - Nabeshima, Toshitaka

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N2 - Background: Tumor necrosis factor-α (TNF-α) is emerging as an important modulator of the function of the central nervous system (CNS). We have demonstrated that TNF-α or Leu-Ile, a TNF-α inducer, inhibits methamphetamine-induced rewarding effects and sensitization. In this study, we investigated the effects of TNF-α or Leu-Ile on morphine (MOR)-induced rewarding effects and sensitization. Methods: Levels of TNF-α messenger RNA (mRNA) and protein were determined by real-time reverse transcription polymerase chain reaction (RT-PCR) and immunohistochemistry. Effects of TNF-α 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-α or Leu-Ile on MOR-induced antinociceptive effect and withdrawal symptoms were examined by hot plate test and naloxone-preciptated withdrawal. Results: Morphine induced TNF-α mRNA expression via dopamine and opioid receptors. Posttreatment with TNF-α or Leu-Ile attenuated the MOR-induced place preference and sensitization even after their development, as well as pretreatment with TNF-α or Leu-Ile blocked them. An inhibitory effect of Leu-Ile on MOR-induced place preference was not observed in TNF-α knockout mice. Tumor necrosis factor-α 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-α inhibits MOR-induced rewarding effect and sensitization by regulating extracellular dopamine levels, and Leu-Ile inhibits them via the induction of TNF-α.

AB - Background: Tumor necrosis factor-α (TNF-α) is emerging as an important modulator of the function of the central nervous system (CNS). We have demonstrated that TNF-α or Leu-Ile, a TNF-α inducer, inhibits methamphetamine-induced rewarding effects and sensitization. In this study, we investigated the effects of TNF-α or Leu-Ile on morphine (MOR)-induced rewarding effects and sensitization. Methods: Levels of TNF-α messenger RNA (mRNA) and protein were determined by real-time reverse transcription polymerase chain reaction (RT-PCR) and immunohistochemistry. Effects of TNF-α 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-α or Leu-Ile on MOR-induced antinociceptive effect and withdrawal symptoms were examined by hot plate test and naloxone-preciptated withdrawal. Results: Morphine induced TNF-α mRNA expression via dopamine and opioid receptors. Posttreatment with TNF-α or Leu-Ile attenuated the MOR-induced place preference and sensitization even after their development, as well as pretreatment with TNF-α or Leu-Ile blocked them. An inhibitory effect of Leu-Ile on MOR-induced place preference was not observed in TNF-α knockout mice. Tumor necrosis factor-α 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-α inhibits MOR-induced rewarding effect and sensitization by regulating extracellular dopamine levels, and Leu-Ile inhibits them via the induction of TNF-α.

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