title: Impairment of opiate-mediated behaviors by the selective TRPV1 antagonist SB366791.
abstract: Transient receptor potential vanilloid type 1 (TRPV1), the archetypal member of the vanilloid TRP family, was initially identified as the receptor for capsaicin, the pungent ingredient in hot chili peppers. We previously demonstrated that TRPV1 in the dorsal striatum significantly contributes to morphine reward by using the conditioned place preference paradigm in mice; however, it is unknown whether TRPV1 has the same effect in other reward models. In this study, we investigated the role of TRPV1 in morphine reward by using a self-administration paradigm in rats. We found that treatment with a selective TRPV1 antagonist, SB366791, significantly decreased morphine self-administration on a fixed-ratio 1 schedule or a progressive ratio schedule of reinforcement. In addition, treatment with another selective TRPV1 antagonist, AMG9810, not only significantly prevented morphine self-administration but also prevented morphine-induced c-fos expression in the nucleus accumbens. Furthermore, administration of SB366791 decreased an anxiolytic-like effect during the morphine abstinence period. Moreover, treatment with SB366791 significantly decreased morphine-priming reinstatement. Taken together, our findings suggest that blockade of TRPV1 receptors could provide an approach to limiting morphine addiction.
authors.affiliation: Department of Pharmacology, School of Pharmacy, Sungkyunkwan University, Korea.
authors.forename: Shi-Xun
authors.initials: SX
authors.lastname: Ma
authors.affiliation: Department of Pharmacology, School of Pharmacy, Sungkyunkwan University, Korea.
authors.forename: Seung-Hwan
authors.initials: SH
authors.lastname: Kwon
authors.affiliation: Department of Pharmacology, School of Pharmacy, Sungkyunkwan University, Korea.
authors.forename: Jee-Yeon
authors.initials: JY
authors.lastname: Seo
authors.affiliation: Department of Pharmacology, School of Pharmacy, Sungkyunkwan University, Korea.
authors.forename: Ji-Young
authors.initials: JY
authors.lastname: Hwang
authors.affiliation: Department of Pharmacology, School of Pharmacy, Sungkyunkwan University, Korea.
authors.forename: Sa-Ik
authors.initials: SI
authors.lastname: Hong
authors.affiliation: Neuropsychopharmacology and Neurotoxicology Program, College of Pharmacy, Kangwon National University, Korea.
authors.forename: Hyoung-Chun
authors.initials: HC
authors.lastname: Kim
authors.affiliation: Department of Pharmacology, School of Pharmacy, Sungkyunkwan University, Korea.
authors.forename: Seok-Yong
authors.initials: SY
authors.lastname: Lee
authors.affiliation: Department of Pharmacology, School of Pharmacy, Sungkyunkwan University, Korea.
authors.forename: Choon-Gon
authors.initials: CG
authors.lastname: Jang
mesh_terms: D000701:Analgesics, Opioid / Q000008:administration & dosage*; D000813:Anilides / Q000494:pharmacology*; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D015153:Blotting, Western; D002934:Cinnamates / Q000494:pharmacology*; D008297:Male; D023421:Models, Animal; D009020:Morphine / Q000008:administration & dosage*; D009714:Nucleus Accumbens / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D012201:Reward
chemical_list: D000701:Analgesics, Opioid; D000813:Anilides; D002934:Cinnamates; C477659:N-(3-methoxyphenyl)-4-chlorocinnamanilide; D009020:Morphine
keywords: SB366791; TRPV1; addiction; morphine; self-administration