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Investigation of the involvement of central ghrelin signalling in methamphetamine dependence using behavioural and molecular methods
Lapka, Marek ; Šustková, Magdaléna (advisor) ; Votava, Martin (referee) ; Amchová, Petra (referee)
v anglickém jazyce Interest in appetite-inducing peptide hormones, such as ghrelin, is gradually increasing. There is a growing number of publications dealing with the involvement of this orexigenic peptide in the mechanisms of obesity and various addictive behaviours, not excluding addiction to stimulant substances including methamphetamine. Central ghrelin signaling appears to play an important role in addictive behavior, and in the processing of memory traces. Recently, antagonism of the ghrelin receptor for growth hormone secretion (GHS-R1A) has been proposed as a promising tool for the still unsatisfactory treatment of methamphetamine addiction. Premedication with a commonly used experimental GHS-R1A antagonist, the triazole derivative, JMV2959, significantly reduced the rewarding and reinforcing effects of methamphetamine in several animal models of addiction. However, the molecular aspects of GHS-R1A involvement in specific brain regions related to the addiction process remain unclear. This work demonstrates that acute and subchronic (4 days) administration of JMV2959 alone, at doses significantly effective in addiction models (1 and 3 mg/kg intraperitoneally), had no effect on memory functions tested in the Morris water maze in rats, as well as no significant effects on molecular markers...
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Opioids as model drugs for exploring the mechanism underlying the development of drug dependence
Trojánková, Nikola ; Novotný, Jiří (advisor) ; Hejnová, Lucie (referee)
The aim of this bachelor thesis was to gather knowledge about the mechanisms of addiction, where opioids served as model compounds. Opioids are substances commonly used to treat acute and severe pain as in cancer treatment. However, long-term administration of these drugs killing, after a time reaches the ceiling, which is caused by rapid onset of analgesic tolerance and the slow development of tolerance to the secondary side effects. To achieve the same effect has to be constantly increasing dose, leading to the emergence and development of dependence. Mechanisms of drug addiction are still not fully elucidated, but recent studies agree that a very significant role in these events are membrane-bound opioid receptors and adenylyl cyclase signaling system that regulates intracellular levels of cAMP and CREB and FosB as transcription factors. Very important are the so-called epigenetic mechanisms, such as post-translational modification of histones and DNA or gene expression.
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