scholarly journals The Role of Orexin-1 Receptor Signaling in Demand for the Opioid Fentanyl

2019 ◽  
Author(s):  
Jennifer E. Fragale ◽  
Caroline B. Pantazis ◽  
Morgan H. James ◽  
Gary Aston-Jones
Keyword(s):  
Behavioral Economics ◽  
Drug Addiction ◽  
Abuse Liability ◽  
Demand Elasticity ◽  
Potential Treatment ◽  
Treatment Target ◽  
On Demand ◽  
Abused Drugs ◽  
Increasing Demand

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.

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 ◽  
...  
Keyword(s):  
Drug Addiction ◽  
Addiction Treatment ◽  
Early Stage ◽  
Human Society ◽  
Growth Hormone Secretagogue Receptor ◽  
Comprehensive Overview ◽  
Growth Hormone Secretagogue ◽  
Addictive Drugs ◽  
Abused Drugs

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.

Treatment of ebola and other infectious diseases: melatonin “goes viral”

2020 ◽  
Vol 3 (1) ◽  
pp. 43-57 ◽  
Author(s):  
Russel J Reiter ◽  
Qiang Ma ◽  
Ramaswamy Sharma
Keyword(s):  
Mortality Rate ◽  
Infectious Diseases ◽  
Hemorrhagic Shock ◽  
Safety Profile ◽  
Ebola Virus ◽  
Viral Infections ◽  
Virus Disease ◽  
Attractive Potential ◽  
Potential Treatment

This review summarizes published reports on the utility of melatonin as a treatment for virus-mediated diseases. Of special note are the data related to the role of melatonin in influencing Ebola virus disease. This infection and deadly condition has no effective treatment and the published works documenting the ability of melatonin to attenuate the severity of viral infections generally and Ebola infection specifically are considered. The capacity of melatonin to prevent one of the major complications of an Ebola infection, i.e., the hemorrhagic shock syndrome, which often contributes to the high mortality rate, is noteworthy. Considering the high safety profile of melatonin, the fact that it is easily produced, inexpensive and can be self-administered makes it an attractive potential treatment for Ebola virus pathology.  

Prawne aspekty eutanazji w Holandii

2016 ◽  
Vol 14 (3) ◽  
pp. 243-253
Author(s):  
Grzegorz Stefanowicz
Keyword(s):  
The Netherlands ◽  
Assisted Suicide ◽  
Public Authority ◽  
Dutch Society ◽  
On Demand ◽  
Limited Length ◽  
The Law ◽  
Death On Demand ◽  
The Way

This article undertakes to show the way that has led to the statutory decriminalization of euthanasia-related murder and assisted suicide in the Kingdom of the Netherlands. It presents the evolution of the views held by Dutch society on the euthanasia related practice, in the consequence of which death on demand has become legal after less than thirty years. Due attention is paid to the role of organs of public authority in these changes, with a particular emphasis put on the role of the Dutch Parliament – the States General. Because of scarcity of space and limited length of the article, the change in the attitudes toward euthanasia, which has taken place in the Netherlands, is presented in a synthetic way – from the first discussions on admissibility of a euthanasia-related murder carried out in the 1970s, through the practice of killing patients at their request, which was against the law at that time, but with years began more and more acceptable, up to the statutory decriminalization of euthanasia by the Dutch Parliament, made with the support of the majority of society.

Plasma Serotonin in Heart Failure: Possible Marker and Potential Treatment Target

2017 ◽  
Vol 26 (5) ◽  
pp. 442-449 ◽  
Author(s):  
Ahmed M. Selim ◽  
Nitasha Sarswat ◽  
Iosif Kelesidis ◽  
Muhammad Iqbal ◽  
Ramesh Chandra ◽  
...  
Keyword(s):  
Heart Failure ◽  
Potential Treatment ◽  
Treatment Target ◽  
Plasma Serotonin

scholarly journals The Paradoxical Effect Hypothesis of Abused Drugs in a Rat Model of Chronic Morphine Administration

2021 ◽  
Vol 10 (15) ◽  
pp. 3197
Author(s):  
Yinghao Yu ◽  
Alan Bohan He ◽  
Michelle Liou ◽  
Chenyin Ou ◽  
Anna Kozłowska ◽  
...  
Keyword(s):  
Drug Addiction ◽  
Basolateral Amygdala ◽  
Neural Substrates ◽  
Plasma Corticosterone ◽  
High Plasma ◽  
Paradoxical Effect ◽  
Chronic Morphine ◽  
Morphine Administration ◽  
Abused Drugs ◽  
Effect Hypothesis

A growing body of studies has recently shown that abused drugs could simultaneously induce the paradoxical effect in reward and aversion to influence drug addiction. However, whether morphine induces reward and aversion, and which neural substrates are involved in morphine’s reward and aversion remains unclear. The present study first examined which doses of morphine can simultaneously produce reward in conditioned place preference (CPP) and aversion in conditioned taste aversion (CTA) in rats. Furthermore, the aversive dose of morphine was determined. Moreover, using the aversive dose of 10 mg/kg morphine tested plasma corticosterone (CORT) levels and examined which neural substrates were involved in the aversive morphine-induced CTA on conditioning, extinction, and reinstatement. Further, we analyzed c-Fos and p-ERK expression to demonstrate the paradoxical effect—reward and aversion and nonhomeostasis or disturbance by morphine-induced CTA. The results showed that a dose of more than 20 mg/kg morphine simultaneously induced reward in CPP and aversion in CTA. A dose of 10 mg/kg morphine only induced the aversive CTA, and it produced higher plasma CORT levels in conditioning and reacquisition but not extinction. High plasma CORT secretions by 10 mg/kg morphine-induced CTA most likely resulted from stress-related aversion but were not a rewarding property of morphine. For assessments of c-Fos and p-ERK expression, the cingulate cortex 1 (Cg1), prelimbic cortex (PrL), infralimbic cortex (IL), basolateral amygdala (BLA), nucleus accumbens (NAc), and dentate gyrus (DG) were involved in the morphine-induced CTA, and resulted from the aversive effect of morphine on conditioning and reinstatement. The c-Fos data showed fewer neural substrates (e.g., PrL, IL, and LH) on extinction to be hyperactive. In the context of previous drug addiction data, the evidence suggests that morphine injections may induce hyperactivity in many neural substrates, which mediate reward and/or aversion due to disturbance and nonhomeostasis in the brain. The results support the paradoxical effect hypothesis of abused drugs. Insight from the findings could be used in the clinical treatment of drug addiction.

scholarly journals Investigating collaborative and mobility networks: reflections on the core missions of universities

2021 ◽  
Author(s):  
Zsolt Tibor Kosztyán ◽  
Beáta Fehérvölgyi ◽  
Tibor Csizmadia ◽  
Kinga Kerekes
Keyword(s):  
Social Progress ◽  
Industry Funding ◽  
Multilayer Network ◽  
The Core ◽  
Funding Agencies ◽  
Valid Assessment ◽  
Increasing Demand ◽  
Public Money ◽  
University Performance

AbstractGiven the significant role of universities in economic growth and social progress as well as the increasing demand for greater transparency regarding the use of public money, a valid assessment of university performance has become crucial for various stakeholders, including government, industry, funding agencies, and society at large. Contemporary assessments still focus solely on universities’ properties, thereby failing to capture their network relations. To overcome this limitation, this paper proposes a multilayer network-based method to measure the embeddedness of universities in collaboration and mobility networks. This method has several advantages: first, it is relevant for HEIs’ core missions, introducing a new dimension complementary to the existing rankings; second, it is size invariant; and last but not least, it is fully transparent. The proposed multilayer network approach enables the integration of further networks, which creates opportunities for a more comprehensive assessment of universities’ performance in achieving their core missions.

scholarly journals The role of anticipation in drug addiction and reward

2013 ◽  
pp. 1
Author(s):  
Matt Field ◽  
Pawel Jedras ◽  
Andrew Jones
Keyword(s):  
Drug Addiction
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