National Repository of Grey Literature 6 records found  Search took 0.01 seconds. 
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,...
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...
Gene expression pattern in the adult brain of the experimental rat after prenatal exposure to methamphetamine
Tomášková, Anežka ; Černá, Marie (advisor) ; Rudá, Jana (referee)
Introduction: Methamphetamine is a drug frequently taken by drug-addicted pregnant women and happens to be one of the most commonly used drugs in the Czech Republic. This drug passes easily through a placental barrier into the fetus. Thus it can negatively affect not only the mother but also the prenatal development of her offspring. Objectives: This research aims to provide a general screening of gene expression in selected regions of the F1 generation of the brain prenatally affected by methamphetamine, to verify whether exposure to methamphetamine affects the generation of offspring of exposed females at the level of gene expression in selected regions of the brain, and to valuate possible changes in gene expression. Methods: In selected parts of the brain, collected from a rat, the microarray hybridization and the real-time PCR were set to evaluate express changes in the expression of selected genes. Results: Statistical analysis of the microarray hybridization did not show a significantly altered gene expression in the tested genes. Only boundary values for 13 genes were measured, which were further tested by the real-time PCR. After a statistic evaluation of the real-time PCR, the significantly altered expression was found in 2 genes. The notably changed expression of DRD3 and TACR3 genes...
Effects of Neurotransmission-Modulating Multipotent Compounds in Pharmacological Animal Models of Cognitive Deficit
Chvojková, Markéta ; Valeš, Karel (advisor) ; Kuchař, Martin (referee) ; Rudá, Jana (referee)
In preclinical research on Alzheimer's disease pharmacotherapy, attention is paid to multipotent compounds, enabling intensification of the effect by targeting multiple pathophysiological mechanisms. The aim of the thesis was to assess the effect of multipotent compounds and combination therapy in models of cognitive deficit in the rat. The mechanism of action of the tested compounds was modulation of neurotransmitter systems. The aim of the first part of the study was to compare the effect of experimental monotherapy and combination therapy with an N-methyl-D-aspartate (NMDA) receptor antagonist and a γ-aminobutyric acid type A (GABAA) receptor positive modulator in the trimethyltin-induced model. Superiority of the combination therapy was proven by histological analysis of hippocampal neurodegeneration; however, it did not reach statistical significance in the cognitive test. The other part of the thesis focused on multipotent tacrine derivatives. We demonstrated a positive effect of 6- chlorotacrine-6-nitrobenzothiazole hybrid, as well as 6-chlorotacrine-L-tryptophan hybrid, acting as acetylcholinesterase inhibitors, in the scopolamine-induced model of cognitive deficit. Besides, we demonstrated a low risk of serious side effects of other tacrine derivatives acting as NMDA receptor antagonists....
Gene expression pattern in the adult brain of the experimental rat after prenatal exposure to methamphetamine
Tomášková, Anežka ; Černá, Marie (advisor) ; Rudá, Jana (referee)
Introduction: Methamphetamine is a drug frequently taken by drug-addicted pregnant women and happens to be one of the most commonly used drugs in the Czech Republic. This drug passes easily through a placental barrier into the fetus. Thus it can negatively affect not only the mother but also the prenatal development of her offspring. Objectives: This research aims to provide a general screening of gene expression in selected regions of the F1 generation of the brain prenatally affected by methamphetamine, to verify whether exposure to methamphetamine affects the generation of offspring of exposed females at the level of gene expression in selected regions of the brain, and to valuate possible changes in gene expression. Methods: In selected parts of the brain, collected from a rat, the microarray hybridization and the real-time PCR were set to evaluate express changes in the expression of selected genes. Results: Statistical analysis of the microarray hybridization did not show a significantly altered gene expression in the tested genes. Only boundary values for 13 genes were measured, which were further tested by the real-time PCR. After a statistic evaluation of the real-time PCR, the significantly altered expression was found in 2 genes. The notably changed expression of DRD3 and TACR3 genes...
Prenatal exposure to methamphetamine and its effect on the gene expression in the selected parts of the brains of experimental rats
Tomášková, Anežka ; Zoubková, Hana (advisor) ; Rudá, Jana (referee)
Introduction: Methamphetamine is a drug frequently abused by drug-addicted pregnant women and also one of the mostcommonly used drugs in the CzechRepublic. This drug passes easily through a placental barrier into the fetus. Thus it can negatively affect not only the mother but also the prenatal development of her offspring. Objectives: In the framework of the grant project GA CR: 14-03708S, the long-term effects of prenatal exposure to methamphetamine were detected. It was determined whether the prenatal methamphetamine exposure affects the generation of offspring of exposed females at the level of gene expression of genes in specific regions of the brain, striatum, hippocampus and prefrontal cortex. Methods: In the selected parts of the brain, which were removed from the rat, the microarray hybridization and the real-time PCR to express changes in expression of selected genes were performed. Results: Statistical analysis of microarray hybridization did not show the significantly altered gene expression in tested genes significantly. Only boundary values for 13 genes were measured, which were further tested by real-time PCR.After a statistic evaluation of real-time PCR, the significantly altered expression was found in 2 genes. The significantly changed expression of DRD3 and TACR3 genes was found...

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