title: Ghrelin receptor antagonism of morphine-induced accumbens dopamine release and behavioral stimulation in rats.
abstract: OBJECTIVE
  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: Department of Pharmacology, Third Faculty of Medicine, Charles University, Ruska 87, Prague 10, 100 34, Czech Republic, magdalena.sustkova@lf3.cuni.cz.
authors: Magdalena
authors: M
authors: Sustkova-Fiserova
authors: Pavel
authors: P
authors: Jerabek
authors: Tereza
authors: T
authors: Havlickova
authors: Petr
authors: P
authors: Kacer
authors: Miloslav
authors: M
authors: Krsiak
mesh_terms: D015102:3,4-Dihydroxyphenylacetic Acid / Q000378:metabolism; D000701:Analgesics, Opioid / Q000008:administration & dosage / Q000494:pharmacology; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D004298:Dopamine / Q000031:analogs & derivatives / Q000378:metabolism* / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D054439:Ghrelin / Q000378:metabolism; D005998:Glycine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D006719:Homovanillic Acid / Q000494:pharmacology; D008297:Male; D017551:Microdialysis; D009020:Morphine / Q000008:administration & dosage / Q000494:pharmacology*; D009714:Nucleus Accumbens / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D054440:Receptors, Ghrelin / Q000037:antagonists & inhibitors* / Q000378:metabolism; D012201:Reward; D013239:Stereotyped Behavior / Q000187:drug effects; D014230:Triazoles / Q000008:administration & dosage / Q000494:pharmacology*
chemical_list: D000701:Analgesics, Opioid; D054439:Ghrelin; C569751:N-(1-(4-(4-methoxybenzyl)-5-phenethyl-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)-2-aminoacetamide; D054440:Receptors, Ghrelin; D014230:Triazoles; D015102:3,4-Dihydroxyphenylacetic Acid; D009020:Morphine; C001746:3-methoxytyramine; D005998:Glycine; D004298:Dopamine; D006719:Homovanillic Acid