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The role of ghrelin signalling in the neurobiological mechanisms of rewarding effects of cannabinoids and opioids
Charalambous, Chrysostomos ; Šustková, Magdaléna (advisor) ; Rudá, Jana (referee) ; Petrásek, Tomáš (referee)
Background: Ghrelin, an orexigenic appetite stimulating peptide, in addition to promoting energy balance, contributes to the rewarding effects associated with overeating. It also seems to play an important role in the rewarding/reinforcing effects of alcohol and addictive stimulants. The involvement of the ghrelin mechanisms in cannabinoid and opioid misuse and addiction have been under-researched. Aims: The principal aim of this research thesis was to investigate whether the pretreatment with the growth hormone secretagogue receptor 1A (GHS-R1A) antagonist (JMV2959) could reduce the cannabinoid receptor type 1 (CB1R) agonist WIN55,212-2-induced dopamine efflux in the nucleus accumbens shell (NACSh), which is considered a crucial trigger impulse of the addiction process. Also, test whether JMV2959 can influence the WIN55,212-2 and fentanyl-induced effects on the endocannabinoids N-arachidonoylethanolamine (anandamide) and 2-arachidonoylglycerol (2-AG) and the gama-aminobutyric acid (GABA) content in the NACSh, and in extend, to specify the involvement of GHS-R1A located in the ventral tegmental area (VTA) and the NACSh in the observed accumbens changes. Furthermore, to test whether the JMV2959 pretreatment could reduce the cannabinoid [tetrahydrocannabinol (THC) and WIN55,212-2] induced behavioural...
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