Activation of serotonin 5-HT2C receptor suppresses behavioral sensitization and naloxone-precipitated withdrawal symptoms in morphine-dependent mice. (February 2016)

• Record Type: Journal Article
• Authors: Zhang, Gongliang; Wu, Xian; Zhang, Yong-Mei; Liu, Huan; Jiang, Qin; Pang, Gang; Tao, Xinrong; Dong, Liuyi; Stackman, Robert W.
• Is Part Of: Neuropharmacology. Volume 101(2016)
• Page Start: 246
• Page End: 254
• Publication Date: 2016-02
• Subjects: Serotonin -- 5-HT2C receptor -- Morphine -- Behavioral sensitization -- Withdrawal -- Ventral tegmental area -- Nucleus accumbens -- Locus coeruleus; Neuropsychopharmacology -- Periodicals; Autonomic Agents -- Periodicals; Neuropsychopharmacologie -- Périodiques; Neuropsychopharmacology; Periodicals; Electronic journals; 615.78
• DOI: 10.1016/j.neuropharm.2015.09.031
• Languages: English
• ISSNs: 0028-3908

Abstract

Abstract: Opioid abuse and dependence have evolved into an international epidemic as a significant clinical and societal problem with devastating consequences. Repeated exposure to the opioid, for example morphine, can induce profound, long-lasting behavioral sensitization and physical dependence, which are thought to reflect neuroplasticity in neural circuitry. Central serotonin (5-HT) neurotransmission participates in the development of dependence on and the expression of withdrawal from morphine. Serotonin 5-HT2C receptor (5-HT2C R) agonists suppress psychostimulant nicotine or cocaine-induced behavioral sensitization and drug-seeking behavior; however, the impact of 5-HT2C R agonists on behaviors relevant to opioid abuse and dependence has not been reported. In the present study, the effects of 5-HT2C R activation on the behavioral sensitization and naloxone-precipitated withdrawal symptoms were examined in mice underwent repeated exposure to morphine. Male mice received morphine (10 mg/kg, s.c.) to develop behavioral sensitization. Lorcaserin, a 5-HT2C R agonist, prevented the induction and expression, but not the development, of morphine-induced behavioral sensitization. Another cohort of mice received increasing doses of morphine over a 7-day period to induce morphine-dependence. Pretreatment of lorcaserin, or the positive control clonidine (an alpha 2-adrenoceptor agonist), ameliorated the naloxone-precipitated withdrawal symptoms. SB 242084, a selective 5-HT2C R antagonist, prevented the lorcaserin-mediated suppression of behavioral sensitization and withdrawal. Chronic morphine treatment was associated with an increase in the expression of 5-HT2C R protein in the ventral tegmental area, locus coeruleus and nucleus accumbens. These findings suggest that 5-HT2C R can modulate behavioral sensitization and withdrawal in morphine-dependent mice, and the activation of 5-HT2C R may represent a new avenue for the treatment of opioid addiction. Highlights: Activation of 5-HT2C R suppresses the induction and expression of behavioral sensitization induced by morphine. Activation of 5-HT2C R ameliorates naloxone-precipitated withdrawal symptoms in morphine-dependent mice. Chronic morphine exposure increases 5-HT2C R expression in ventral tegmental area, locus coeruleus and nucleus accumbens. 5-HT2C R may be a drug target for preventing the abuse and dependence of opioid.