CC-Chemokine Ligand 2 Facilitates Conditioned Place Preference to Methamphetamine Through the Activation of Dopamine Systems
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- Wakida Naoki
- Department of Pharmacology, Wakayama Medical University, Japan
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- Kiguchi Norikazu
- Department of Pharmacology, Wakayama Medical University, Japan
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- Saika Fumihiro
- Department of Pharmacology, Wakayama Medical University, Japan
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- Nishiue Hideki
- Department of Pharmacology, Wakayama Medical University, Japan
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- Kobayashi Yuka
- Department of Pharmacology, Wakayama Medical University, Japan
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- Kishioka Shiroh
- Department of Pharmacology, Wakayama Medical University, Japan
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Methamphetamine addiction is characterized by drug craving caused by stimulation of the reward system. Because neuroinflammation underlies several neurological disorders, we investigated whether CC-chemokine ligand 2 (CCL2) participates in the methamphetamine dependence using mice. Upregulation of CCL2 but not CC-chemokine receptor 2 (CCR2), a dominant receptor for CCL2, mRNA in both the prefrontal cortex (PFC) and nucleus accumbens (NAC) was observed after methamphetamine (3 mg/kg, s.c.) administration. Using immunohistochemistry, high CCL2 protein levels localized to neurons in the PFC and NAC. In the conditioned place preference (CPP) test, methamphetamine (0.3 – 3 mg/kg, s.c.) induced a CPP, reflecting psychic dependence on methamphetamine, in a dose-dependent manner. The CPP to methamphetamine was attenuated by RS504393 (1 mg/kg, s.c.), a CCR2 antagonist. Moreover, methamphetamine increased phosphorylated tyrosine hydroxylase (pTH) levels in the ventral tegmental area (VTA). Increased levels of pTH in the VTA by methamphetamine was also suppressed by RS504393. Furthermore, intracerebroventricular injection of recombinant CCL2 increased pTH levels in the VTA. Taken together, we demonstrate that activation of dopamine neurons, which enhances reward-system activity, via the CCL2-CCR2 axis plays a crucial role in psychic dependence on methamphetamine. Novel treatments targeting this machinery may be effective for drug addiction.
収録刊行物
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- Journal of Pharmacological Sciences
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Journal of Pharmacological Sciences 125 (1), 68-73, 2014
公益社団法人 日本薬理学会
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詳細情報 詳細情報について
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- CRID
- 1390001205180325120
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- NII論文ID
- 130003391520
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- NII書誌ID
- AA11806667
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- COI
- 1:CAS:528:DC%2BC2cXptlSisLk%3D
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- ISSN
- 13478648
- 13478613
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- NDL書誌ID
- 025463152
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- PubMed
- 24748435
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- 本文言語コード
- en
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- データソース種別
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- JaLC
- NDL
- Crossref
- PubMed
- CiNii Articles
- KAKEN
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- 抄録ライセンスフラグ
- 使用不可