Blockade of TRPV1 Inhibits Methamphetamine-induced Rewarding Effects
| Autor: | Shi-Xun Ma, Seok-Yong Lee, Choon-Gon Jang, Kwang-Wook Lee, Sunmee Wee, Yu-Hua Tian, George F. Koob |
|---|---|
| Rok vydání: | 2018 |
| Předmět: |
Male
0301 basic medicine Microdialysis Dopamine Conditioning Classical lcsh:Medicine TRPV Cation Channels Striatum Pharmacology Nucleus accumbens Article Nucleus Accumbens Methamphetamine Mice 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Reward Conditioning Psychological medicine Animals lcsh:Science Dopamine transporter Mice Knockout Dopamine Plasma Membrane Transport Proteins Multidisciplinary biology lcsh:R Conditioned place preference Mice Inbred C57BL 030104 developmental biology nervous system chemistry biology.protein lcsh:Q Central Nervous System Stimulants Female Capsazepine psychological phenomena and processes 030217 neurology & neurosurgery Signal Transduction medicine.drug |
| Zdroj: | Scientific Reports Scientific Reports, Vol 8, Iss 1, Pp 1-12 (2018) |
| ISSN: | 2045-2322 |
| DOI: | 10.1038/s41598-018-19207-2 |
| Popis: | Methamphetamine (MAP) is the most widely used psychostimulant in the world, but the exact mechanisms underlying MAP addiction are not yet fully understood. Recent studies have identified the distribution of TRPV1 in several brain regions that are related to drug addiction, including nucleus accumbens (NAc) and dorsal striatum (DSt). In the present study, we performed conditioned place preference (CPP) and self-administration tests to examine the effects of capsazepine (CPZ) and SB366791 (SB) on MAP reward. We found that both CPZ and SB significantly inhibited MAP-induced CPP and self-administration; in contrast, TRPV1 knock-out (KO) mice did not develop MAP-induced CPP. Real-time RT-PCR, Western blot and quantitative autoradiographic tests showed up-regulation of TRPV1 mRNA and protein expression in the NAc and/or DSt regions of mice exhibiting MAP-induced CPP. In addition, an in vivo microdialysis experiment showed that CPZ dramatically reduced dopamine (DA) levels in the NAc region of MAP-treated mice. Furthermore, attenuated dopamine transporter (DAT) binding levels in the NAc and DSt regions of MAP-induced CPP mice were reversed by CPZ. Together, these data suggest that TRPV1 plays an important role in MAP reward via the modulation of DA release and DAT density, thereby providing a novel therapeutic target for MAP addiction. |
| Databáze: | OpenAIRE |
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