Ghrelin and endocannabinoids participation in morphine-induced effects in the rat nucleus accumbens

Sustkova-Fiserova, Magdalena; Jerabek, Pavel; Havlickova, Tereza; Syslová, Kamila; Kačer, Petr

doi:10.1007/s00213-015-4119-3

Cited by 29 publications

(33 citation statements)

References 57 publications

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“…As expected, fentanyl induced typical significant biphasic (inhibition-stimulation) behavioural changes in the rats, as illustrated in Figure 7 , in accordance with our previous studies with morphine [ 16 , 17 , 21 , 85 ]. The fentanyl-induced changes were more dynamic in comparison with morphine and the behaviour returned to almost normal control parameters at the end of the experiment.…”

Section: Resultssupporting

confidence: 91%

“…Our results for the first time indicate significant involvement of GHS-R1As within the VTA and NAC in opioid/fentanyl-induced changes in the NACSh endocannabinoid AEA and 2-AG as well as GABA extracellular concentrations. Concerning endocannabinoids, the present results extent and particularize our previous study with morphine and systemic JMV2959 pre-treatment [ 17 ]. Fentanyl is considered as a µ-receptor-selective agonist, 100-fold more potent than morphine, mediating its reinforcing properties through both VTA as well as NAC µ-receptors [ 28 , 31 , 74 ].…”

Section: Discussionsupporting

confidence: 81%

“…It has also been described [ 52 ] that during the heroin self-administration N -arachidonoylethanolamine (anandamide, AEA) levels were significantly enhanced and simultaneously 2-arachidonoylglycerol (2-AG) levels significantly decreased in the dialysates from the NACSh. This is in accordance with our previous microdialysis study in rats [ 17 ] where we observed a significant AEA increase and significant 2-AG decrease in the NACSh dialysates after acute morphine dose as well as when morphine was administered during prolonged abstinence from repeated morphine. In addition, Vigano et al [ 54 ] measurements of accumbens 2-AG and AEA contents post mortem after sub-chronic morphine administration in rats showed AEA increase and 2-AG decrease.…”

Section: Introductionsupporting

confidence: 93%

“…In addition to hypothalamus, the central GHS-R1As are expressed in important reward related areas including striatum, nucleus accumbens (NAC), amygdala, prefrontal cortex, hippocampus, and ventral tegmental area (VTA) [ 5 , 6 , 7 , 8 , 9 , 10 , 11 , 12 ]. Available literature involving ghrelin in opioid abuse and addiction is still limited and inconclusive [ 13 , 14 , 15 , 16 , 17 ]. The self-administration study of Maric et al [ 13 ] showed that ghrelin administered intracerebroventricularly (i.c.v.)…”

Section: Introductionmentioning

confidence: 99%

“…In our previous study, we have documented a significant interaction between ghrelin and endocannabinoids in the morphine-induced changes in the NACSh [ 17 ]. Premedication with JMV2959 before morphine, which was administered in acute doses or in a challenge dose during prolonged abstinence from chronic morphine, dose-dependently reversed the morphine-induced AEA increase in the NACSh leading to a significant AEA drop.…”

Section: Introductionmentioning

confidence: 99%

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Alterations in Rat Accumbens Endocannabinoid and GABA Content during Fentanyl Treatment: The Role of Ghrelin

Sustkova-Fiserova

Charalambous

Havlickova

et al. 2017

IJMS

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The opioid-induced rise of extracellular dopamine, endocannabinoid anandamide and γ-aminobutyric acid (GABA) concentrations triggered by opioids in the nucleus accumbens shell (NACSh) most likely participate in opioid reward. We have previously demonstrated that systemic administration of ghrelin antagonist (JMV2959) significantly decreased morphine-induced dopamine and anandamide (N-arachidonoylethanolamine, AEA) increase in the NACSh. Fentanyl is considered as a µ-receptor-selective agonist. The aim of this study was to test whether JMV2959, a growth hormone secretagogue receptor (GHS-R1A) antagonist, can influence the fentanyl-induced effects on anandamide, 2-arachidonoylglycerol (2-AG) and GABA in the NACSh and specify the involvement of GHS-R1A located in the ventral tegmental area (VTA) and nucleus accumbens (NAC). Using in vivo microdialysis in rats, we have found that pre-treatment with JMV2959 reversed dose dependently fentanyl-induced anandamide increases in the NACSh, resulting in a significant AEA decrease and intensified fentanyl-induced decreases in accumbens 2-AG levels, with both JMV2959 effects more expressed when administered into the NACSh in comparison to the VTA. JMV2959 pre-treatment significantly decreased the fentanyl-evoked accumbens GABA efflux and reduced concurrently monitored fentanyl-induced behavioural stimulation. Our current data encourage further investigation to assess if substances affecting GABA or endocannabinoid concentrations and action, such as GHS-R1A antagonists, can be used to prevent opioid-seeking behaviour.

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