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Research on ghrelin mechanisms for the prevention of relapse in cannabinoid addiction
Charalambous, Chrysostomos ; Šustková, Magdaléna (advisor) ; Vaculín, Šimon (referee) ; Rudá, Jana (referee)
Background: Cannabis and cannabinoids are frequently used for recreational and therapeutic purposes, but people tend to overlook the associated risks that comes with them. Cannabinoid- associated use disorders and dependence are alarmingly increasing, and an effective treatment is currently lacking. Recently, the growth hormone secretagogue receptor (GHSR1A) antagonism was proposed as a promising mechanism for drug addiction therapy. However, the role of GHS- R1A and its endogenous ligand ghrelin in cannabinoid abuse remains unclear. Aim: The principal aim of this research thesis was to further investigate whether the GHS-R1A antagonist JMV2959 could reduce the WIN55,212-2 intravenous self-administration (IVSA) and the tendency to relapse, but also reduce the tetrahydrocannabinol (THC)-induced conditioned place preference (CPP). Methods: In a rat model, the intravenous self-administration directly measured the rat's response to the reinforcement effects of WIN55,212-2 as spontaneous drug-seeking and consumption with pretreatments of GHS-R1A antagonist/JMV2959 or saline. Further, the behavioural changes in rats were observed on the conditioned place preference apparatus which monitored the influence of JMV2959 on the THC effects. Findings: Following the ongoing WIN55,212-2 self-administration,...
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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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