Ghrelin receptor antagonism of morphine-induced conditioned place preference and behavioral and accumbens dopaminergic sensitization in rats
Jazyk angličtina Země Anglie, Velká Británie Médium print-electronic
Typ dokumentu časopisecké články
PubMed
28958601
DOI
10.1016/j.neuint.2017.09.013
PII: S0197-0186(16)30485-5
Knihovny.cz E-zdroje
- Klíčová slova
- Accumbens, Addiction, Dopamine, Ghrelin, JMV2959 (PubChem CID: 16114404), Morphine, Morphine hydrochloride (PubChem CID: 5288826), Sensitization,
- MeSH
- dopamin * metabolismus MeSH
- glycin analogy a deriváty farmakologie MeSH
- krysa rodu Rattus MeSH
- mikrodialýza metody MeSH
- morfin aplikace a dávkování antagonisté a inhibitory MeSH
- nucleus accumbens účinky léků metabolismus MeSH
- operantní podmiňování účinky léků fyziologie MeSH
- opioidní analgetika aplikace a dávkování antagonisté a inhibitory MeSH
- potkani Wistar MeSH
- receptory ghrelinu antagonisté a inhibitory metabolismus MeSH
- triazoly farmakologie MeSH
- zvířata MeSH
- Check Tag
- krysa rodu Rattus MeSH
- mužské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- dopamin * MeSH
- glycin MeSH
- morfin MeSH
- N-(1-(4-(4-methoxybenzyl)-5-phenethyl-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)-2-aminoacetamide MeSH Prohlížeč
- opioidní analgetika MeSH
- receptory ghrelinu MeSH
- triazoly MeSH
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. Recently we substantiated in rats that ghrelin growth hormone secretagogue receptors (GHS-R1A) appear to be involved in acute opioid-induced changes in the mesolimbic dopaminergic system associated with the reward processing. The aim of the present study was to ascertain whether a ghrelin antagonist (JMV2959) was able to inhibit morphine-induced biased conditioned place preference and challenge-morphine-induced accumbens dopaminergic sensitization and behavioral sensitization in adult male rats. In the place preference model, the rats were conditioned for 8 days with morphine (10 mg/kg s.c.). On the experimental day, JMV2959 (3 and 6 mg/kg i.p.) or saline were administered before testing. We used in vivo microdialysis to determine changes of dopamine and its metabolites in the nucleus accumbens in rats following challenge-morphine dose (5 mg/kg s.c.) with or without JMV2959 (3 and 6 mg/kg i.p.) pretreatment, administered on the 12th day of spontaneous abstinence from morphine repeated treatment (5 days, 10-40 mg/kg). Induced behavioral changes were simultaneously monitored. Pretreatment with JMV2959 significantly and dose dependently reduced the morphine-induced conditioned place preference and significantly and dose dependently reduced the challenge-morphine-induced dopaminergic sensitization and affected concentration of by-products associated with dopamine metabolism in the nucleus accumbens. JMV2959 pretreatment also significantly reduced challenge-morphine-induced behavioral sensitization. Our present data suggest that GHS-R1A antagonists deserve to be further investigated as a novel treatment strategy for opioid addiction.
Citace poskytuje Crossref.org
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