Dissociable role of tumor necrosis factor alpha gene deletion in methamphetamine self-administration and cue-induced relapsing behavior in mice

Yijin Yan, Atsumi Nitta, Takenao Koseki, Kiyofumi Yamada, Toshitaka Nabeshima

研究成果: Article

3 引用 (Scopus)

抄録

Rationale: During the development of addiction, addictive drugs induce transient and long-lasting changes in the brain including expression of endogenous molecules and alteration of morphological structure. Of the altered endogenous molecules, some facilitate but others slow the development of drug addiction. Previously, we have reported that tumor necrosis factor alpha (TNF-α) is a critical molecule among endogenous anti-addictive modulators using animal models of drug-conditioned place preference and drug discrimination. Objectives: Does targeted deletion of the TNF-α gene in mice affect methamphetamine (METH) self-administration, motivation to self-administer METH, cue-induced reinstatement of METH-seeking behavior, and food reinforcement or seeking behavior? Methods: Both METH self-administration and reinstatement of drug-seeking behavior and food self-delivery and food-seeking behavior were measured in TNF-α (-/-) and wild-type mice. Results: There were an upward shift of dose responses to METH self-administration under a fixed ratio schedule of reinforcement and higher breaking points under a progressive ratio schedule of reinforcement in TNF-α knockout (TNF-α (-/-)) mice as compared with wild-type mice. There was no significant difference in cue-induced reinstatement of METH-seeking behavior, food-maintained operant behavior, motivation to natural food, and cue-induced food-seeking behavior between TNF-α (-/-) and wild-type mice. Conclusion: TNF-α affects METH self-administration and motivation to self-administer METH but contributes to neither METH-associated cue-induced relapsing behavior nor food reward and food-seeking behavior. TNF-α may be explored for use as a diagnostic biomarker for the early stage of drug addiction.

元の言語English
ページ(範囲)427-436
ページ数10
ジャーナルPsychopharmacology
221
発行部数3
DOI
出版物ステータスPublished - 01-06-2012
外部発表Yes

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Self Administration
Methamphetamine
Gene Deletion
Cues
Tumor Necrosis Factor-alpha
Food
Substance-Related Disorders
Motivation
Reinforcement Schedule
Drug-Seeking Behavior
Reward
Knockout Mice
Pharmaceutical Preparations
Animal Models
Biomarkers
Brain

All Science Journal Classification (ASJC) codes

  • Pharmacology

これを引用

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title = "Dissociable role of tumor necrosis factor alpha gene deletion in methamphetamine self-administration and cue-induced relapsing behavior in mice",
abstract = "Rationale: During the development of addiction, addictive drugs induce transient and long-lasting changes in the brain including expression of endogenous molecules and alteration of morphological structure. Of the altered endogenous molecules, some facilitate but others slow the development of drug addiction. Previously, we have reported that tumor necrosis factor alpha (TNF-α) is a critical molecule among endogenous anti-addictive modulators using animal models of drug-conditioned place preference and drug discrimination. Objectives: Does targeted deletion of the TNF-α gene in mice affect methamphetamine (METH) self-administration, motivation to self-administer METH, cue-induced reinstatement of METH-seeking behavior, and food reinforcement or seeking behavior? Methods: Both METH self-administration and reinstatement of drug-seeking behavior and food self-delivery and food-seeking behavior were measured in TNF-α (-/-) and wild-type mice. Results: There were an upward shift of dose responses to METH self-administration under a fixed ratio schedule of reinforcement and higher breaking points under a progressive ratio schedule of reinforcement in TNF-α knockout (TNF-α (-/-)) mice as compared with wild-type mice. There was no significant difference in cue-induced reinstatement of METH-seeking behavior, food-maintained operant behavior, motivation to natural food, and cue-induced food-seeking behavior between TNF-α (-/-) and wild-type mice. Conclusion: TNF-α affects METH self-administration and motivation to self-administer METH but contributes to neither METH-associated cue-induced relapsing behavior nor food reward and food-seeking behavior. TNF-α may be explored for use as a diagnostic biomarker for the early stage of drug addiction.",
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Dissociable role of tumor necrosis factor alpha gene deletion in methamphetamine self-administration and cue-induced relapsing behavior in mice. / Yan, Yijin; Nitta, Atsumi; Koseki, Takenao; Yamada, Kiyofumi; Nabeshima, Toshitaka.

:: Psychopharmacology, 巻 221, 番号 3, 01.06.2012, p. 427-436.

研究成果: Article

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T1 - Dissociable role of tumor necrosis factor alpha gene deletion in methamphetamine self-administration and cue-induced relapsing behavior in mice

AU - Yan, Yijin

AU - Nitta, Atsumi

AU - Koseki, Takenao

AU - Yamada, Kiyofumi

AU - Nabeshima, Toshitaka

PY - 2012/6/1

Y1 - 2012/6/1

N2 - Rationale: During the development of addiction, addictive drugs induce transient and long-lasting changes in the brain including expression of endogenous molecules and alteration of morphological structure. Of the altered endogenous molecules, some facilitate but others slow the development of drug addiction. Previously, we have reported that tumor necrosis factor alpha (TNF-α) is a critical molecule among endogenous anti-addictive modulators using animal models of drug-conditioned place preference and drug discrimination. Objectives: Does targeted deletion of the TNF-α gene in mice affect methamphetamine (METH) self-administration, motivation to self-administer METH, cue-induced reinstatement of METH-seeking behavior, and food reinforcement or seeking behavior? Methods: Both METH self-administration and reinstatement of drug-seeking behavior and food self-delivery and food-seeking behavior were measured in TNF-α (-/-) and wild-type mice. Results: There were an upward shift of dose responses to METH self-administration under a fixed ratio schedule of reinforcement and higher breaking points under a progressive ratio schedule of reinforcement in TNF-α knockout (TNF-α (-/-)) mice as compared with wild-type mice. There was no significant difference in cue-induced reinstatement of METH-seeking behavior, food-maintained operant behavior, motivation to natural food, and cue-induced food-seeking behavior between TNF-α (-/-) and wild-type mice. Conclusion: TNF-α affects METH self-administration and motivation to self-administer METH but contributes to neither METH-associated cue-induced relapsing behavior nor food reward and food-seeking behavior. TNF-α may be explored for use as a diagnostic biomarker for the early stage of drug addiction.

AB - Rationale: During the development of addiction, addictive drugs induce transient and long-lasting changes in the brain including expression of endogenous molecules and alteration of morphological structure. Of the altered endogenous molecules, some facilitate but others slow the development of drug addiction. Previously, we have reported that tumor necrosis factor alpha (TNF-α) is a critical molecule among endogenous anti-addictive modulators using animal models of drug-conditioned place preference and drug discrimination. Objectives: Does targeted deletion of the TNF-α gene in mice affect methamphetamine (METH) self-administration, motivation to self-administer METH, cue-induced reinstatement of METH-seeking behavior, and food reinforcement or seeking behavior? Methods: Both METH self-administration and reinstatement of drug-seeking behavior and food self-delivery and food-seeking behavior were measured in TNF-α (-/-) and wild-type mice. Results: There were an upward shift of dose responses to METH self-administration under a fixed ratio schedule of reinforcement and higher breaking points under a progressive ratio schedule of reinforcement in TNF-α knockout (TNF-α (-/-)) mice as compared with wild-type mice. There was no significant difference in cue-induced reinstatement of METH-seeking behavior, food-maintained operant behavior, motivation to natural food, and cue-induced food-seeking behavior between TNF-α (-/-) and wild-type mice. Conclusion: TNF-α affects METH self-administration and motivation to self-administer METH but contributes to neither METH-associated cue-induced relapsing behavior nor food reward and food-seeking behavior. TNF-α may be explored for use as a diagnostic biomarker for the early stage of drug addiction.

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