Publications by authors named "Marek Lapka"

Central ghrelin signaling seems to play important role in addiction as well as memory processing. Antagonism of the growth hormone secretagogue receptor (GHS-R1A) has been recently proposed as a promising tool for the unsatisfactory drug addiction therapy. However, molecular aspects of GHS-R1A involvement in specific brain regions remain unclear.

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Ascorbic acid is a well-described molecule which acts as a cofactor in many reactions and mediates a variety of biological functions. Despite its simple structure, vitamin C has a wide range of interesting effects that bring enormous potential to the clinical practice. The article summarizes available data on efficacy and safety in oncology.

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Drug addiction causes constant serious health, social, and economic burden within the human society. The current drug dependence pharmacotherapies, particularly relapse prevention, remain limited, unsatisfactory, unreliable for opioids and tobacco, and even symptomatic for stimulants and cannabinoids, thus, new more effective treatment strategies are researched. The antagonism of the growth hormone secretagogue receptor type A (GHS-R1A) has been recently proposed as a novel alcohol addiction treatment strategy, and it has been intensively studied in experimental models of other addictive drugs, such as nicotine, stimulants, opioids and cannabinoids.

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Cannabis/cannabinoids are widely used for recreational and therapy purposes, but their risks are largely disregarded. However, cannabinoid-associated use disorders and dependence are alarmingly increasing and an effective treatment is lacking. Recently, the growth hormone secretagogue receptor (GHSR1A) antagonism was proposed as a promising mechanism for drug addiction therapy.

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Article Synopsis
  • The endocannabinoid system and ghrelin signaling are interconnected and play key roles in food intake and the brain's reward/reinforcement pathways, particularly in regions like the hypothalamus and nucleus accumbens.
  • A study investigated the effects of a GHS-R1A antagonist (JMV2959) on dopamine release in the nucleus accumbens when combined with a CB1R agonist (WIN55,212-2), finding that JMV2959 effectively reduced dopamine levels associated with the addiction process.
  • The results suggest that the ghrelin/GHS-R1A system is significantly involved in the rewarding effects of cannabinoids, as it alters various neurotransmitter levels and reduces behavioral stimulation linked to cannabinoid use.
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The extended occurrence of fentanils abuse associated with the dramatic increase in opioid fatal overdoses and dependence strongly emphasizes insufficiencies in opioid addiction treatment. Recently, the growth hormone secretagogue receptor (GHS-R1A) antagonism was proposed as a promising mechanism for drug addiction therapy. However, the role of GHS-R1A and its endogenous ligand ghrelin in opioid abuse is still unclear.

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Methamphetamine abuse imposes a significant burden on individuals and society worldwide, and an effective therapy of methamphetamine addiction would provide distinguished social benefits. Ghrelin significantly participates in reinforcing neurobiological mechanisms of stimulants, including amphetamines; thus, ghrelin antagonism is proposed as a promising addiction treatment. The aim of our study was to elucidate whether the pretreatment with growth hormone secretagogue receptor (GHS-R1A) antagonist, substance JMV2959, could reduce the methamphetamine intravenous self-administration (IVSA) and the tendency to relapse, and whether JMV2959 could reduce or prevent methamphetamine-induced conditioned place preference (CPP) in rats.

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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 (-arachidonoylethanolamine, AEA) increase in the NACSh. Fentanyl is considered as a µ-receptor-selective agonist.

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An increasing number of studies over the past few years have demonstrated ghrelin's role in alcohol, cocaine and nicotine abuse. However, the role of ghrelin in opioid effects has rarely been examined. Recently we substantiated in rats that ghrelin growth hormone secretagogue receptors (GHS-R1A) appear to be involved in acute opioid-induced changes in the mesolimbic dopaminergic system associated with the reward processing.

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