Activation of serotonin 5-HT2C receptor suppresses behavioral sensitization and naloxone-precipitated withdrawal symptoms in heroin-treated mice

NEUROSCIENCE LETTERS

卷:607

Article

Wu, Xian¹  Pang, Gang¹  Zhang, Yong-Mei²  Li, Guangwu¹  Xu, Shengchun¹  Dong, Liuyi¹  Stackman, Robert W., Jr.^3,4  Zhang, Gongliang^1,3,4 

[1] Anhui Med Univ, Coll Basic Med, Hefei 230032, Anhui, Peoples R China

[2] Xuzhou Med Coll, Coll Anesthesiol, Jiangsu Prov Key Lab Anesthesiol, Xuzhou 221002, Jiangsu, Peoples R China

[3] Florida Atlantic Univ, Dept Psychol, Jupiter, FL 33458 USA

[4] Florida Atlantic Univ, Life Sci Initiat, Jupiter, FL 33458 USA

关键词: Serotonin;    5-HT2C receptor;    Heroin;    Behavioral sensitization;    Withdrawal;   

DOI  :  10.1016/j.neulet.2015.09.013

来源: Elsevier

【 摘 要 】

Abuse and dependence to heroin has evolved into a global epidemic as a significant clinical and societal problem with devastating consequences. Repeated exposure to heroin can induce long-lasting behavioral sensitization and withdrawal. Pharmacological activation of 5-HT2C receptors (5-HT(2C)Rs) suppresses psychostimulant-induced drug-seeking and behavioral sensitization. The present study examined the effect of a selective 5-HT2CR agonist lorcaserin on behavioral sensitization and naloxone-precipitated withdrawal symptoms in heroin-treated mice. Male mice received heroin (1.0 mg/kg, s.c.) twice a day for 3 days and then drug treatment was suspended for 5 days. On day 9, a challenge dose of heroin (1.0 mg/kg) was administered to examine the expression of behavioral sensitization. Lorcaserin administered during the development, withdrawal or expression stage suppressed heroin-induced behavioral sensitization on day 9. Another cohort of mice received increasing doses of heroin over a 4.5-day period. Lorcaserin, or the positive control clonidine (an alpha 2-adrenoceptor agonist) suppressed naloxone-precipitated withdrawal symptoms in heroin-treated mice. These findings suggest that activation of 5-HT(2C)R5 suppresses behavioral sensitization and withdrawal in heroin-treated mice. Thus, pharmacological activation of 5-HT(2C)Rs may represent a new avenue for the treatment of heroin addiction. (C) 2015 Elsevier Ireland Ltd. All rights reserved.

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