title: Activation of serotonin 5-HT(2C) receptor suppresses behavioral sensitization and naloxone-precipitated withdrawal symptoms in heroin-treated mice.
abstract: 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-HT2CRs) 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 α2-adrenoceptor agonist) suppressed naloxone-precipitated withdrawal symptoms in heroin-treated mice. These findings suggest that activation of 5-HT2CRs suppresses behavioral sensitization and withdrawal in heroin-treated mice. Thus, pharmacological activation of 5-HT2CRs may represent a new avenue for the treatment of heroin addiction.
authors.affiliation: College of Basic Medicine, Anhui Medical University, 81 Meishan Road, Hefei, Anhui 230032, China.
authors.forename: Xian
authors.initials: X
authors.lastname: Wu
authors.affiliation: College of Basic Medicine, Anhui Medical University, 81 Meishan Road, Hefei, Anhui 230032, China.
authors.forename: Gang
authors.initials: G
authors.lastname: Pang
authors.affiliation: Jiangsu Province Key Laboratory of Anesthesiology; College of Anesthesiology, Xuzhou Medical College, Xuzhou, Jiangsu 221002, China.
authors.forename: Yong-Mei
authors.initials: YM
authors.lastname: Zhang
authors.affiliation: College of Basic Medicine, Anhui Medical University, 81 Meishan Road, Hefei, Anhui 230032, China.
authors.forename: Guangwu
authors.initials: G
authors.lastname: Li
authors.affiliation: College of Basic Medicine, Anhui Medical University, 81 Meishan Road, Hefei, Anhui 230032, China.
authors.forename: Shengchun
authors.initials: S
authors.lastname: Xu
authors.affiliation: College of Basic Medicine, Anhui Medical University, 81 Meishan Road, Hefei, Anhui 230032, China.
authors.forename: Liuyi
authors.initials: L
authors.lastname: Dong
authors.affiliation: Department of Psychology, Florida Atlantic University and the Life Science Initiative at FAU, 5353 Parkside Drive, Jupiter, FL 33458, USA.
authors.forename: Robert W
authors.initials: RW
authors.lastname: Stackman
authors.affiliation: College of Basic Medicine, Anhui Medical University, 81 Meishan Road, Hefei, Anhui 230032, China.|Department of Psychology, Florida Atlantic University and the Life Science Initiative at FAU, 5353 Parkside Drive, Jupiter, FL 33458, USA.
authors.forename: Gongliang
authors.initials: G
authors.lastname: Zhang
mesh_terms: D058647:Adrenergic alpha-2 Receptor Agonists / Q000494:pharmacology; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D001552:Benzazepines / Q000494:pharmacology; D000697:Central Nervous System Stimulants / Q000009:adverse effects*; D003000:Clonidine / Q000494:pharmacology; D003932:Heroin / Q000009:adverse effects*; D008297:Male; D051379:Mice; D009043:Motor Activity / Q000187:drug effects; D009270:Naloxone / Q000494:pharmacology*; D044405:Receptor, Serotonin, 5-HT2C / Q000378:metabolism*; D058826:Serotonin 5-HT2 Receptor Agonists / Q000494:pharmacology* / Q000627:therapeutic use; D013375:Substance Withdrawal Syndrome / Q000188:drug therapy / Q000378:metabolism* / Q000523:psychology
chemical_list: D058647:Adrenergic alpha-2 Receptor Agonists; D001552:Benzazepines; D000697:Central Nervous System Stimulants; D044405:Receptor, Serotonin, 5-HT2C; D058826:Serotonin 5-HT2 Receptor Agonists; D009270:Naloxone; C506658:lorcaserin; D003932:Heroin; D003000:Clonidine
keywords: 5-HT(2C) receptor; Behavioral sensitization; Heroin; Serotonin; Withdrawal