mGlu5: A double-edged sword for aversive learning related therapeutics

Neuroanatomy and Behaviour ◽

10.35430/nab.2021.e16 ◽

2021 ◽

Vol 3 ◽

pp. e16

Author(s):

Shawn Zheng Kai Tan ◽

Jee Hyun Kim

Keyword(s):

Anxiety Disorders ◽

Therapeutic Potential ◽

Age Factors ◽

Preclinical Studies ◽

Aversive Learning ◽

Future Studies ◽

Metabotropic Glutamate ◽

Pharmacological Targets ◽

Potential Applications

Aversive memories underlie many types of anxiety disorders. One area of research to more effectively treat anxiety disorders has therefore been identifying pharmacological targets to affect memory processes. Among these targets, the metabotropic glutamate 5 receptor (mGlu5) has received attention due to the availability of drugs to utilize its role in learning and memory. In this review, we highlight preclinical studies examining the role of mGlu5 at various stages of aversive learning and its inhibition via extinction in order to gain a better understanding of its therapeutic potential. We suggest that mGlu5 has distinct roles at different stages of memory that not only makes it a tricky target, but a double-edged sword as a therapeutic. However, the selective involvement of mGlu5 in different memory stages allows for certain precision that could be harnessed clinically. We therefore suggest potential applications, limitations, and pitfalls when considering use of mGlu5 modulators as therapeutics. In addition, we recommend future studies to address important gaps in this literature, such as sex and age factors in light of anxiety disorders being more prevalent in those demographics.

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The role of the metabotropic glutamate receptor 5 in nicotine addiction

CNS Spectrums ◽

10.1017/s1092852920001704 ◽

2020 ◽

pp. 1-6

Author(s):

Funda Akkus ◽

Sylvia Terbeck ◽

Connor J. Haggarty ◽

Valerie Treyer ◽

Janan J. Dietrich ◽

...

Keyword(s):

Glutamate Receptor ◽

Clinical Studies ◽

Metabotropic Glutamate Receptor ◽

Therapeutic Potential ◽

Nicotine Addiction ◽

Metabotropic Glutamate Receptor 5 ◽

Metabotropic Glutamate ◽

Nicotine Abuse ◽

Preclinical And Clinical Studies

Abstract This review summarizes the evidence for the potential involvement of metabotropic glutamate receptor 5 (mGluR5) in the development of nicotine addiction. Nicotine is consumed worldwide and is highly addictive. Previous research has extensively investigated the role of dopamine in association with reward learning and addiction, which has provided strong evidence for the involvement of dopaminergic neuronal circuitry in nicotine addiction. More recently, researchers focused on glutamatergic transmission after nicotine abuse, and its involvement in the reinforcing and rewarding effects of nicotine addiction. A number of robust preclinical and clinical studies have shown mGluR5 signaling as a facilitating mechanism of nicotine addiction and nicotine withdrawal. Specifically, clinical studies have illustrated lower cortical mGluR5 density in smokers compared to nonsmokers in the human brain. In addition, mGluR5 might selectively regulate craving and withdrawal. This suggests that mGluR5 could be a key receptor in the development of nicotine addiction and therefore clinical trials to examine the therapeutic potential of mGluR5 agents could help to contribute to reduce nicotine addiction in society.

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Exploring the Role of Dissociation Dimensions in Obsessive Compulsive Disorder

European Psychiatry ◽

10.1016/j.eurpsy.2016.01.1826 ◽

2016 ◽

Vol 33 (S1) ◽

pp. S496-S496

Author(s):

A. Pozza ◽

N. Giaquinta ◽

D. Dèttore

Keyword(s):

Anxiety Disorders ◽

Obsessive Compulsive Disorder ◽

Healthy Controls ◽

Obsessive Compulsive ◽

Future Studies ◽

Compulsive Disorder ◽

Dissociative Experiences ◽

Dissociative Amnesia ◽

Competing Interest

IntroductionIn the last decade, accumulating evidence has been produced on the role of dissociation in Obsessive Compulsive Disorder (OCD). Understanding which dissociation dimensions are specific to OCD could suggest the integration of therapeutic strategies for dissociation in the treatment of patients with OCD.ObjectivesThe current study explored the role of dissociation in a sample of patients with OCD, patients with anxiety disorders and healthy controls with the aim to understand which dissociation dimensions could be specific to OCD.MethodOne hundred seventy-one participants were included in the study (56% females, mean age = 35.96, SD = 12.61), of which 52 were patients with primary OCD, 59 were patients with Anxiety Disorders (AD), and 60 were healthy controls. The Dissociative Experiences Scale (DES), Beck Depression Inventory-II (BDI-II), Beck Anxiety Inventory (BAI), Yale-Brown Obsessive Compulsive Scale (Y-BOCS) were administered.ResultsPatients with OCD had significantly higher dissociative amnesia symptoms than patients with AD and health controls (F = 6.08, P < 0.01) and higher depersonalization/derealization symptoms than healthy controls but not than patients with AD. Patients with OCD did not report significantly higher dissociative absorption than healthy controls and patients with AD.ConclusionsStrategies targeting dissociative amnesia and depersonalization/derealization symptoms in OCD are discussed. Future studies should examine which OCD subtypes are more strongly associated to dissociation dimensions.Disclosure of interestThe authors have not supplied their declaration of competing interest.

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Targeting Adenosine Receptors: A Potential Pharmacological Avenue for Acute and Chronic Pain

International Journal of Molecular Sciences ◽

10.3390/ijms21228710 ◽

2020 ◽

Vol 21 (22) ◽

pp. 8710

Author(s):

Fabrizio Vincenzi ◽

Silvia Pasquini ◽

Pier Andrea Borea ◽

Katia Varani

Keyword(s):

Chronic Pain ◽

Adenosine Receptors ◽

Therapeutic Potential ◽

G Protein Coupled Receptors ◽

Preclinical Studies ◽

Allosteric Modulators ◽

Antinociceptive Effects ◽

Pain Regulation ◽

G Protein Coupled

Adenosine is a purine nucleoside, responsible for the regulation of multiple physiological and pathological cellular and tissue functions by activation of four G protein-coupled receptors (GPCR), namely A1, A2A, A2B, and A3 adenosine receptors (ARs). In recent years, extensive progress has been made to elucidate the role of adenosine in pain regulation. Most of the antinociceptive effects of adenosine are dependent upon A1AR activation located at peripheral, spinal, and supraspinal sites. The role of A2AAR and A2BAR is more controversial since their activation has both pro- and anti-nociceptive effects. A3AR agonists are emerging as promising candidates for neuropathic pain. Although their therapeutic potential has been demonstrated in diverse preclinical studies, no AR ligands have so far reached the market. To date, novel pharmacological approaches such as adenosine regulating agents and allosteric modulators have been proposed to improve efficacy and limit side effects enhancing the effect of endogenous adenosine. This review aims to provide an overview of the therapeutic potential of ligands interacting with ARs and the adenosinergic system for the treatment of acute and chronic pain.

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Mesophyll conductance: the leaf corridors for photosynthesis

Biochemical Society Transactions ◽

10.1042/bst20190312 ◽

2020 ◽

Vol 48 (2) ◽

pp. 429-439 ◽

Cited By ~ 3

Author(s):

Jorge Gago ◽

Danilo M. Daloso ◽

Marc Carriquí ◽

Miquel Nadal ◽

Melanie Morales ◽

...

Keyword(s):

Molecular Mechanisms ◽

Current Knowledge ◽

Main Role ◽

Mesophyll Conductance ◽

Future Studies ◽

Cell Structures ◽

Leaf Tissues ◽

Change Framework ◽

Chloroplast Stroma

Besides stomata, the photosynthetic CO2 pathway also involves the transport of CO2 from the sub-stomatal air spaces inside to the carboxylation sites in the chloroplast stroma, where Rubisco is located. This pathway is far to be a simple and direct way, formed by series of consecutive barriers that the CO2 should cross to be finally assimilated in photosynthesis, known as the mesophyll conductance (gm). Therefore, the gm reflects the pathway through different air, water and biophysical barriers within the leaf tissues and cell structures. Currently, it is known that gm can impose the same level of limitation (or even higher depending of the conditions) to photosynthesis than the wider known stomata or biochemistry. In this mini-review, we are focused on each of the gm determinants to summarize the current knowledge on the mechanisms driving gm from anatomical to metabolic and biochemical perspectives. Special attention deserve the latest studies demonstrating the importance of the molecular mechanisms driving anatomical traits as cell wall and the chloroplast surface exposed to the mesophyll airspaces (Sc/S) that significantly constrain gm. However, even considering these recent discoveries, still is poorly understood the mechanisms about signaling pathways linking the environment a/biotic stressors with gm responses. Thus, considering the main role of gm as a major driver of the CO2 availability at the carboxylation sites, future studies into these aspects will help us to understand photosynthesis responses in a global change framework.

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Motives for Social Isolation Following a Negative Emotional Episode

Swiss Journal of Psychology ◽

10.1024/1421-0185/a000211 ◽

2018 ◽

Vol 77 (3) ◽

pp. 127-131

Author(s):

Gérald Delelis ◽

Véronique Christophe

Keyword(s):

Social Isolation ◽

Social Affiliation ◽

Semantic Categorization ◽

Future Studies ◽

Cognitive Regulation ◽

Emotional Event ◽

Regulation Strategies ◽

Emotional Events

Abstract. After experiencing an emotional event, people either seek out others’ presence (social affiliation) or avoid others’ presence (social isolation). The determinants and effects of social affiliation are now well-known, but social psychologists have not yet thoroughly studied social isolation. This study aims to ascertain which motives and corresponding regulation strategies participants report for social isolation following negative emotional events. A group of 96 participants retrieved from memory an actual negative event that led them to temporarily socially isolate themselves and freely listed up to 10 motives for social isolation. Through semantic categorization of the 423 motives reported by the participants, we found that “cognitive clarification” and “keeping one’s distance” – that is, the need for cognitive regulation and the refusal of socioaffective regulation, respectively – were the most commonly and quickly reported motives for social isolation. We discuss the findings in terms of ideas for future studies aimed at clarifying the role of social isolation in health situations.

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