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Publication : Blockade of TRPV1 Inhibits Methamphetamine-induced Rewarding Effects.

First Author  Tian YH Year  2018
Journal  Sci Rep Volume  8
Issue  1 Pages  882
PubMed ID  29343767 Mgi Jnum  J:260218
Mgi Id  MGI:6148406 Doi  10.1038/s41598-018-19207-2
Citation  Tian YH, et al. (2018) Blockade of TRPV1 Inhibits Methamphetamine-induced Rewarding Effects. Sci Rep 8(1):882
abstractText  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.
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