RATIONALE AND OBJECTIVES: Ghrelin, an orexigenic (appetite stimulating) peptide activates binding sites in the ventral tegmental area (a structure linked with the neural reward system) allowing it to participate in reward-seeking behavior. An increasing number of studies over the past few years have demonstrated ghrelin's role in alcohol, cocaine, and nicotine abuse. However, the role of ghrelin, in opioid effects, has rarely been examined. The aim of the present study was to ascertain whether a ghrelin antagonist (JMV2959) was able to inhibit markers of morphine-induced activation of the neural reward system, namely morphine-induced increase of dopamine in the nucleus accumbens and behavioral changes in rats. METHODS: We used in vivo microdialysis to determine changes of dopamine and its metabolites in the nucleus accumbens shell in rats following morphine (MO, 5, 10 mg/kg s.c.) administration with and without ghrelin antagonist pretreatment (JMV2959, 3, 6 mg/kg i.p., 20 min before MO). Induced behavioral changes were simultaneously monitored. RESULTS: JMV2959 significantly and dose dependently reduced MO-induced dopamine release in the nucleus accumbens shell and affected concentration of by-products associated with dopamine metabolism: 3-methoxytyramine (3-MT), 3,4-dihydroxyphenylacetic acid (DOPAC), and homovanillic acid (HVA). JMV2959 pretreatment also significantly reduced MO-induced behavioral stimulation, especially stereotyped behavior. CONCLUSIONS: Ghrelin secretagogue receptors (GHS-R1A) appear to be involved in the opioid-induced changes in the mesolimbic dopaminergic system associated with the reward processing.
RATIONALE AND OBJECTIVES:Ghrelin, an orexigenic (appetite stimulating) peptide activates binding sites in the ventral tegmental area (a structure linked with the neural reward system) allowing it to participate in reward-seeking behavior. An increasing number of studies over the past few years have demonstrated ghrelin's role in alcohol, cocaine, and nicotine abuse. However, the role of ghrelin, in opioid effects, has rarely been examined. The aim of the present study was to ascertain whether a ghrelin antagonist (JMV2959) was able to inhibit markers of morphine-induced activation of the neural reward system, namely morphine-induced increase of dopamine in the nucleus accumbens and behavioral changes in rats. METHODS: We used in vivo microdialysis to determine changes of dopamine and its metabolites in the nucleus accumbens shell in rats following morphine (MO, 5, 10 mg/kg s.c.) administration with and without ghrelin antagonist pretreatment (JMV2959, 3, 6 mg/kg i.p., 20 min before MO). Induced behavioral changes were simultaneously monitored. RESULTS:JMV2959 significantly and dose dependently reduced MO-induced dopamine release in the nucleus accumbens shell and affected concentration of by-products associated with dopamine metabolism: 3-methoxytyramine (3-MT), 3,4-dihydroxyphenylacetic acid (DOPAC), and homovanillic acid (HVA). JMV2959 pretreatment also significantly reduced MO-induced behavioral stimulation, especially stereotyped behavior. CONCLUSIONS:Ghrelin secretagogue receptors (GHS-R1A) appear to be involved in the opioid-induced changes in the mesolimbic dopaminergic system associated with the reward processing.
Authors: Alfonso Abizaid; Zhong-Wu Liu; Zane B Andrews; Marya Shanabrough; Erzsebet Borok; John D Elsworth; Robert H Roth; Mark W Sleeman; Marina R Picciotto; Matthias H Tschöp; Xiao-Bing Gao; Tamas L Horvath Journal: J Clin Invest Date: 2006-10-19 Impact factor: 14.808
Authors: Davide Quarta; Carla Di Francesco; Sergio Melotto; Laura Mangiarini; Christian Heidbreder; Gael Hedou Journal: Neurochem Int Date: 2008-12-11 Impact factor: 3.921
Authors: Alexandra Labarthe; Oriane Fiquet; Rim Hassouna; Philippe Zizzari; Laurence Lanfumey; Nicolas Ramoz; Dominique Grouselle; Jacques Epelbaum; Virginie Tolle Journal: Front Endocrinol (Lausanne) Date: 2014-10-27 Impact factor: 5.555