Ghrelin and endocannabinoids participation in morphine-induced effects in the rat nucleus accumbens
Language English Country Germany Media print-electronic
Document type Journal Article, Research Support, Non-U.S. Gov't
PubMed
26507196
DOI
10.1007/s00213-015-4119-3
PII: 10.1007/s00213-015-4119-3
Knihovny.cz E-resources
- Keywords
- 2-Arachidonoylglycerol, Acute, Anandamide, Challenge during abstinence, Endocannabinoids, Ghrelin, Microdialysis, Morphine, Neural reward system, Nucleus accumbens shell, Stereotyped behavior,
- MeSH
- Endocannabinoids metabolism physiology MeSH
- Extracellular Space drug effects metabolism MeSH
- Ghrelin physiology MeSH
- Glycerides metabolism MeSH
- Glycine analogs & derivatives pharmacology MeSH
- Rats MeSH
- Arachidonic Acids metabolism MeSH
- Morphine pharmacology MeSH
- Narcotics pharmacology MeSH
- Nucleus Accumbens drug effects metabolism MeSH
- Polyunsaturated Alkamides metabolism MeSH
- Rats, Wistar MeSH
- Receptors, Ghrelin antagonists & inhibitors MeSH
- Receptors, Somatotropin antagonists & inhibitors MeSH
- Stereotyped Behavior drug effects MeSH
- Triazoles pharmacology MeSH
- Dose-Response Relationship, Drug MeSH
- Animals MeSH
- Check Tag
- Rats MeSH
- Male MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Names of Substances
- anandamide MeSH Browser
- Endocannabinoids MeSH
- Ghrelin MeSH
- Glycerides MeSH
- glyceryl 2-arachidonate MeSH Browser
- Glycine MeSH
- Arachidonic Acids MeSH
- Morphine MeSH
- N-(1-(4-(4-methoxybenzyl)-5-phenethyl-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethyl)-2-aminoacetamide MeSH Browser
- Narcotics MeSH
- Polyunsaturated Alkamides MeSH
- Receptors, Ghrelin MeSH
- Receptors, Somatotropin MeSH
- Triazoles MeSH
RATIONALE AND OBJECTIVES: In addition to dopamine, endocannabinoids are thought to participate in neural reward mechanisms of opioids. Number of recent studies suggests crucial involvement of ghrelin in some addictive drugs effects. Our previous results showed that ghrelin participates in morphine-induced changes in the mesolimbic dopaminergic system associated with reward processing. The goal of the present study was to test whether the growth hormone secretagogue receptor (GHS-R1A) antagonist JMV2959 was able to influence morphine-induced effects on anandamide (N-arachidonoylethanolamine, AEA) and 2-arachidonoylglycerol (2-AG) in the nucleus accumbens shell (NACSh). METHODS: We used in vivo microdialysis to determine changes in levels of AEA and 2-AG in the NACSh in rats following (i) an acute morphine dose (5, 10 mg/kg s.c.) with and without JMV2959 pretreatment (3, 6 mg/kg i.p.) or (ii) a morphine challenge dose (5 mg/kg s.c.) with and without JMV2959 (3, 6 mg/kg i.p.) pretreatment, administered during abstinence following repeated doses of morphine (5 days, 10-40 mg/kg). Co-administration of ghrelin (40 ug/kg i.p.) was used to verify the ghrelin mechanisms involvement. RESULTS: Pretreatment with JMV2959 significantly and dose-dependently reversed morphine-induced anandamide increases in the NACSh in both the acute and longer-term models, resulting in a significant AEA decrease. JMV2959 significantly intensified acute morphine-induced decreases in accumbens 2-AG levels and attenuated morphine challenge-induced 2-AG decreases. JMV2959 pretreatment significantly reduced concurrent morphine challenge-induced behavioral sensitization. JMV2959 pretreatment effects were abolished by co-administration of ghrelin. CONCLUSIONS: Our results indicate significant involvement of ghrelin signaling in morphine-induced endocannabinoid changes in the NACSh.
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