scholarly journals The Role of Ghrelin/GHS-R1A Signaling in Nonalcohol Drug Addictions

2022 ◽  
Vol 23 (2) ◽  
pp. 761
Author(s):  
Magdalena Sustkova-Fiserova ◽  
Chrysostomos Charalambous ◽  
Anna Khryakova ◽  
Alina Certilina ◽  
Marek Lapka ◽  
...  

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. The role of ghrelin signaling in these drugs effects has also been investigated. The present review aims to provide a comprehensive overview of preclinical and clinical studies focused on ghrelin’s/GHS-R1A possible involvement in these nonalcohol addictive drugs reinforcing effects and addiction. Although the investigation is still in its early stage, majority of the existing reviewed experimental results from rodents with the addition of few human studies, that searched correlations between the genetic variations of the ghrelin signaling or the ghrelin blood content with the addictive drugs effects, have indicated the importance of the ghrelin’s/GHS-R1As involvement in the nonalcohol abused drugs pro-addictive effects. Further research is necessary to elucidate the exact involved mechanisms and to verify the future potential utilization and safety of the GHS-R1A antagonism use for these drug addiction therapies, particularly for reducing the risk of relapse.

2021 ◽  
Vol 12 ◽  
Author(s):  
Jing Zhao ◽  
Xinyu Du ◽  
Mingzhu Chen ◽  
Shimin Zhu

Relapse to drug seeking after prolonged abstinence is a major problem in the clinical treatment of drug addiction. The use of pharmacological interventions to disrupt established drug reward memories is a promising strategy for the treatment of drug addiction. A growth hormone secretagogue receptor 1 A antagonist, JMV2959, has been shown to reduce morphine-induced conditioned place preference (CPP) in rats within hours of intervention; thus, JMV2959 is a potential candidate for drug addiction treatment. However, the effect of JMV2959 on reconsolidation to disrupt drug seeking remains unknown. In this study, we assessed the effect of JMV2959 on morphine induced memory reconsolidation to inhibit drug seeking after drug withdrawal. Our results showed that the administration of JMV2959 (6 mg/kg) significantly reduced environmental cue induced CPP, which suggested a preventive effect of JMV2959 on morphine induced memory reconsolidation. Additionally, JMV2959 administration significantly altered the locomotor activity and food and water intake but did not significantly alter the natural reward preference. We concluded that JMV2959 may be an effective candidate to treat drug addiction.


Endocrinology ◽  
2011 ◽  
Vol 152 (12) ◽  
pp. 4800-4812 ◽  
Author(s):  
José Córdoba-Chacón ◽  
Manuel D. Gahete ◽  
Ana I. Pozo-Salas ◽  
Antonio J. Martínez-Fuentes ◽  
Luis de Lecea ◽  
...  

Cortistatin (CST) and somatostatin (SST) evolve from a common ancestral gene and share remarkable structural, pharmacological, and functional homologies. Although CST has been considered as a natural SST-analogue acting through their shared receptors (SST receptors 1–5), emerging evidence indicates that these peptides might in fact exert unique roles via selective receptors [e.g. CST, not SST, binds ghrelin receptor growth hormone secretagogue receptor type 1a (GHS-R1a)]. To determine whether the role of endogenous CST is different from SST, we characterized the endocrine-metabolic phenotype of male/female CST null mice (cort−/−) at hypothalamic-pituitary-systemic (pancreas-stomach-adrenal-liver) levels. Also, CST effects on hormone expression/secretion were evaluated in primary pituitary cell cultures from male/female mice and female primates (baboons). Specifically, CST exerted an unexpected stimulatory role on prolactin (PRL) secretion, because both male/female cort−/− mice had reduced PRL levels, and CST treatment (in vivo and in vitro) increased PRL secretion, which could be blocked by a GHS-R1a antagonist in vitro and likely relates to the decreased success of female cort−/− in first-litter pup care at weaning. In contrast, CST inhibited GH and adrenocorticotropin-hormone axes in a gender-dependent fashion. In addition, a rise in acylated ghrelin levels was observed in female cort−/− mice, which were associated with an increase in stomach ghrelin/ghrelin O-acyl transferase expression. Finally, CST deficit uncovered a gender-dependent role of this peptide in the regulation of glucose-insulin homeostasis, because male, but not female, cort−/− mice developed insulin resistance. The fact that these actions are not mimicked by SST and are strongly gender dependent offers new grounds to investigate the hitherto underestimated physiological relevance of CST in the regulation of physiological/metabolic processes.


2009 ◽  
Vol 123 (5) ◽  
pp. 1058-1065 ◽  
Author(s):  
Alexander W. Johnson ◽  
Rebecca Canter ◽  
Michela Gallagher ◽  
Peter C. Holland

2019 ◽  
Vol 21 (4) ◽  
pp. 330-343
Author(s):  
SS Hoseinizadeh ◽  
M Niazi ◽  
M Mehtari Arani ◽  
◽  
◽  
...  

Author(s):  
Gilyana Kazakova ◽  
Tatiana Safronova ◽  
Daniil Golubchikov ◽  
Olga Shevtsova ◽  
Julietta Rau

Materials based on Mg2+-containing phosphates are gaining great relevance in the field of bone tissue repair via regenerative medicine methods. Magnesium ions, together with condensed phosphate ions, play a significant role in the process of bone remodeling, affecting the early stage of bone regeneration through active participation in the process of osteosynthesis. Here we pro-vide a comprehensive overview of the usage of biomaterials based on magnesium phosphate and magnesium calcium phosphate in bone reconstruction. The role of magnesium ions in angiogene-sis, an important process associated with osteogenesis, is considered. Finally, the biological properties of magnesium phosphates for bone regeneration are summarized. They show promis-ing results in terms of use as bone replacement material.


Materials ◽  
2021 ◽  
Vol 14 (17) ◽  
pp. 4857
Author(s):  
Gilyana Kazakova ◽  
Tatiana Safronova ◽  
Daniil Golubchikov ◽  
Olga Shevtsova ◽  
Julietta V. Rau

Materials based on Mg2+-containing phosphates are gaining great relevance in the field of bone tissue repair via regenerative medicine methods. Magnesium ions, together with condensed phosphate ions, play substantial roles in the process of bone remodeling, affecting the early stage of bone regeneration through active participation in the process of osteosynthesis. In this paper we provide a comprehensive overview of the usage of biomaterials based on magnesium phosphate and magnesium calcium phosphate in bone reconstruction. We consider the role of magnesium ions in angiogenesis, which is an important process associated with osteogenesis. Finally, we summarize the biological properties of calcium magnesium phosphates for regeneration of bone.


2020 ◽  
Vol 12 (1) ◽  
pp. 1-20 ◽  
Author(s):  
Zvonko Merkaš ◽  
Davor Perkov ◽  
Vesna Bonin

The purpose of this article is to identify blockchain's role in achieving logistic objectives, with the aim of pointing out the significance of blockchain technology in the digital transformation of logistics and transportation. Implementation of the blockchain technology in combination with IoT elements in logistics and transportation contributes to business process optimization, supply chain traceability and transparency, and significant financial savings. There are limitations as blockchain is at a relatively early stage of development with most projects. Therefore, the approach of theory building from multiple case studies was used. The article provides a comprehensive overview of current blockchain initiatives and use-cases. This article is believed to be the first to address the role of blockchain technology in achieving logistics objectives. Results from this research indicate that blockchain technology contributes to the achievement of logistics objectives.


Author(s):  
Tony D Jung

Pioglitazone is a selective agonist for peroxisome proliferatoractivated receptor gamma (PPARγ) that is currently used for the treatment of type 2 diabetes mellitus. However, recent evidence suggests that the PPARγ pathway may be a promising novel target for drug addiction therapy. There has been considerable evidence with preclinical models of addiction that support pioglitazone’s therapeutic potential for opioid, alcohol, methamphetamine, and cocaine dependence. Although the precise mechanisms remain unclear, these preclinical studies suggest that pioglitazone blocks the excitation of ventral tegmental area dopamine signaling, which is associated with the addictive properties of abused drugs. Recently, clinical studies have also emerged to investigate the role of pioglitazone for drug addiction in humans. Clinical evidence supports preclinical findings that pioglitazone may indeed be beneficial for the treatment of cocaine dependence. Other clinical evidence suggests that pioglitazone may also be effective for nicotine addiction. Further clinical research is needed to investigate pioglitazone’s effects in opioid, alcohol, and methamphetamine addiction. Pioglitazone also has a favourable and safe profile. These findings suggest that pioglitazone may be a novel treatment option for drug dependence in the future. Due to its status as a medication approved by the Food and Drug Administration, there is a potential for accelerated establishment of pioglitazone as an addiction treatment method.


2019 ◽  
Author(s):  
Jennifer E. Fragale ◽  
Caroline B. Pantazis ◽  
Morgan H. James ◽  
Gary Aston-Jones

AbstractThe orexin system is a potential treatment target for drug addiction. Orexin-1 receptor (OxR1) antagonism reduces demand for cocaine and remifentanil indicating that orexin-based therapies may reduce demand for many classes of abused drugs. However, pharmacokinetics vary greatly among opioids and it is unclear if OxR1 antagonism would reduce demand for all opioids, particularly ones with particularly high abuse liability. Here, we establish a behavioral economics (BE) procedure to assess the effects of OxR1 antagonism on demand for the highly abused opioid fentanyl. We also investigate the utility of our novel procedure in predicting OxR1 antagonism efficacy and relapse propensity. The OxR1 antagonist SB-334867 (SB) increased demand elasticity (α; decreased motivation) for fentanyl without affecting preferred consumption of fentanyl at null cost (Qo). Baseline α values predicted SB efficacy, such that SB was most effective at increasing demand elasticity in highly motivated rats. SB also attenuated cue-induced fentanyl seeking and baseline α values predicted the amount of reinstatement behavior. These results highlight the promise of the orexin system as a treatment target for opioid addiction and emphasize the usefulness of BE procedures in the study of opioid abuse.


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