The rostromedial tegmental nucleus gates fat overconsumption through ventral tegmental area output in male rats.

Excessive consumption of palatable foods that are rich in fats and sugars has contributed to the increasing prevalence of obesity worldwide. Similar to addictive drugs, such foods activate the brain's reward circuit, involving mesolimbic dopaminergic projections from the ventral tegmental area (VTA) to the nucleus accumbens (NAc) and the prefrontal cortex. Neuroadaptations occurring in this circuit are hypothesized to contribute to uncontrolled consumption of such foods, a common feature of most of eating disorders and obesity.

Altered reward processing following sucrose bingeing in male and female mice.

Binge eating disorder (BED) is the most prevalent eating disorder associated with multiple adverse health effects, especially mental health issues, including substance use disorders and mood and anxiety disorders. Given these high comorbidities, the objective of our study was to examine whether bingeing behavior would lead to altered perception of reinforcing properties of EtOH and changes in well-being. We used a sucrose bingeing model based on an intermittent access paradigm with a two-bottle choice, without fasting, in male and female mice.

The Role of the Endocannabinoid System in Binge Eating Disorder.

Eating disorders are multifactorial disorders that involve maladaptive feeding behaviors. Binge eating disorder (BED), the most prevalent of these in both men and women, is characterized by recurrent episodes of eating large amounts of food in a short period of time, with a subjective loss of control over eating behavior. BED modulates the brain reward circuit in humans and animal models, which involves the dynamic regulation of the dopamine circuitry.

Hippocampal Cannabinoid 1 Receptors Are Modulated Following Cocaine Self-administration in Male Rats.

Cocaine addiction is a complex pathology inducing long-term neuroplastic changes that, in turn, contribute to maladaptive behaviors. This behavioral dysregulation is associated with transcriptional reprogramming in brain reward circuitry, although the mechanisms underlying this modulation remain poorly understood. The endogenous cannabinoid system may play a role in this process in that cannabinoid mechanisms modulate drug reward and contribute to cocaine-induced neural adaptations.

The endocannabinoid system is modulated in reward and homeostatic brain regions following diet-induced obesity in rats: a cluster analysis approach.

Objectives: Increased availability of high-calorie palatable food in most countries has resulted in overconsumption of these foods, suggesting that excessive eating is driven by pleasure, rather than metabolic need. The behavior contributes to the rise in eating disorders, obesity, and associated pathologies like diabetes, cardiac disease, and cancers. The mesocorticolimbic dopamine and homeostatic circuits are interconnected and play a central role in palatable food intake.

Binge sucrose-induced neuroadaptations: A focus on the endocannabinoid system.

Binge eating, the defining feature of binge eating disorder (BED), is associated with a number of adverse health outcomes as well as a reduced quality of life. Animals, like humans, selectively binge on highly palatable food suggesting that the behaviour is driven by hedonic, rather than metabolic, signals. Given the links to both reward processing and food intake, this study examined the contribution of the endocannabinoid system (ECS) to binge-like eating in rats.

Hippocampal mu opioid receptors are modulated following cocaine self-administration in rat.

Cocaine addiction is a complex pathology induced by long-term brain changes. Understanding the neurochemical changes underlying the reinforcing effects of this drug of abuse is critical for reducing the societal burden of drug addiction. The mu opioid receptor plays a major role in drug reward.

LSP2-9166, an orthosteric mGlu4 and mGlu7 receptor agonist, reduces cocaine self-administration under a progressive ratio schedule in rats.

Cocaine addiction is a serious health issue in Western countries. Despite the regular increase in cocaine consumption across the population, there is no specific treatment for cocaine addiction. Critical roles for glutamate neurotransmission in the rewarding effects of psychostimulants as well as relapse have been suggested and accumulating evidence indicates that targeting mGlu group III receptors could represent a promising strategy to develop therapeutic compounds to treat addiction.

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Founded in 1919, the Society of Biology of Strasbourg (SBS) is a learned society whose purpose is the dissemination and promotion of scientific knowledge in biology. Subsidiary of the Society of Biology, the SBS celebrated its Centenary on Wednesday, the 16th of October 2019 on the Strasbourg University campus and at the Strasbourg City Hall. This day allowed retracing the various milestones of the SBS, through its main strengths, its difficulties and its permanent goal to meet scientific and societal challenges.

Can cocaine-induced neuroinflammation explain maladaptive cocaine-associated memories?

Persistent and intrusive memories define a number of psychiatric disorders, including posttraumatic stress disorder and substance use disorder. In the latter, memory for drug-paired cues plays a critical role in sustaining compulsive drug use as these are potent triggers of relapse. As with many drugs, cocaine-cue associated memory is strengthened across presentations as cues become reliable predictors of drug availability.

Deletion of mu opioid receptors reduces palatable solution intake in a mouse model of binge eating.

Binge eating in humans is driven by hedonic properties of food, suggesting that brain reward systems may contribute to this behaviour. We examined the role of mu opioid receptors (MOP) in binge eating by examining sweet solution intake in mice with genetic deletion of the MOP. Wildtype and MOP knockout mice had 4 hours access to food in the home cage combined with limited (4 hours) access to sucrose (17.

CB1 Agonism Alters Addiction-Related Behaviors in Mice Lacking Mu or Delta Opioid Receptors.

Opioids are powerful analgesics but the clinical utility of these compounds is reduced by aversive outcomes, including the development of affective and substance use disorders. Opioid systems do not function in isolation so understanding how these interact with other neuropharmacological systems could lead to novel therapeutics that minimize withdrawal, tolerance, and emotional dysregulation. The cannabinoid system is an obvious candidate as anatomical, pharmacological, and behavioral studies point to opioid-cannabinoid interactions in the mediation of these processes.

Neuroepigenetics and addictive behaviors: Where do we stand?

Substance use disorders involve long-term changes in the brain that lead to compulsive drug seeking, craving, and a high probability of relapse. Recent findings have highlighted the role of epigenetic regulations in controlling chromatin access and regulation of gene expression following exposure to drugs of abuse. In the present review, we focus on data investigating genome-wide epigenetic modifications in the brain of addicted patients or in rodent models exposed to drugs of abuse, with a particular focus on DNA methylation and histone modifications associated with transcriptional studies.

Mu Opioid Receptors in Gamma-Aminobutyric Acidergic Forebrain Neurons Moderate Motivation for Heroin and Palatable Food.

Background: Mu opioid receptors (MORs) are central to pain control, drug reward, and addictive behaviors, but underlying circuit mechanisms have been poorly explored by genetic approaches. Here we investigate the contribution of MORs expressed in gamma-aminobutyric acidergic forebrain neurons to major biological effects of opiates, and also challenge the canonical disinhibition model of opiate reward.

Methods: We used Dlx5/6-mediated recombination to create conditional Oprm1 mice in gamma-aminobutyric acidergic forebrain neurons.

Inhibition of DNA methyltransferases regulates cocaine self-administration by rats: a genome-wide DNA methylation study.

DNA methylation is a major epigenetic process which regulates the accessibility of genes to the transcriptional machinery. In the present study, we investigated whether modifying the global DNA methylation pattern in the brain would alter cocaine intake by rats, using the cocaine self-administration test. The data indicate that treatment of rats with the DNA methyltransferase inhibitors 5-aza-2'-deoxycytidine (dAZA) and zebularine enhanced the reinforcing properties of cocaine.

Kappa opioid receptor antagonism and chronic antidepressant treatment have beneficial activities on social interactions and grooming deficits during heroin abstinence.

Addiction is a chronic brain disorder that progressively invades all aspects of personal life. Accordingly, addiction to opiates severely impairs interpersonal relationships, and the resulting social isolation strongly contributes to the severity and chronicity of the disease. Uncovering new therapeutic strategies that address this aspect of addiction is therefore of great clinical relevance.

Interactions of the opioid and cannabinoid systems in reward: Insights from knockout studies.

The opioid system consists of three receptors, mu, delta, and kappa, which are activated by endogenous opioid peptides (enkephalins, endorphins, and dynorphins). The endogenous cannabinoid system comprises lipid neuromodulators (endocannabinoids), enzymes for their synthesis and their degradation and two well-characterized receptors, cannabinoid receptors CB1 and CB2. These systems play a major role in the control of pain as well as in mood regulation, reward processing and the development of addiction.

Dissociation of heroin-induced emotional dysfunction from psychomotor activation and physical dependence among inbred mouse strains.

Rationale: Opiate addiction is a brain disorder emerging through repeated intoxication and withdrawal episodes. Epidemiological studies also indicate that chronic exposure to opiates may lead in susceptible individuals to the emergence of depressive symptoms, strongly contributing to the severity and chronicity of addiction. We recently established a mouse model of heroin abstinence, characterized by the development of depressive-like behaviors following chronic heroin exposure.

Delta opioid receptors expressed in forebrain GABAergic neurons are responsible for SNC80-induced seizures.

The delta opioid receptor (DOR) has raised much interest for the development of new therapeutic drugs, particularly to treat patients suffering from mood disorders and chronic pain. Unfortunately, the prototypal DOR agonist SNC80 induces mild epileptic seizures in rodents. Although recently developed agonists do not seem to show convulsant properties, mechanisms and neuronal circuits that support DOR-mediated epileptic seizures remain to be clarified.

A novel anxiogenic role for the delta opioid receptor expressed in GABAergic forebrain neurons.

Background: The delta opioid receptor (DOR) is broadly expressed throughout the nervous system; it regulates chronic pain, emotional responses, motivation, and memory. Neural circuits underlying DOR activities have been poorly explored by genetic approaches. We used conditional mouse mutagenesis to elucidate receptor function in GABAergic neurons of the forebrain.

Distinct mu, delta, and kappa opioid receptor mechanisms underlie low sociability and depressive-like behaviors during heroin abstinence.

Addiction is a chronic disorder involving recurring intoxication, withdrawal, and craving episodes. Escaping this vicious cycle requires maintenance of abstinence for extended periods of time and is a true challenge for addicted individuals. The emergence of depressive symptoms, including social withdrawal, is considered a main cause for relapse, but underlying mechanisms are poorly understood.

15 years of genetic approaches in vivo for addiction research: Opioid receptor and peptide gene knockout in mouse models of drug abuse.

The endogenous opioid system is expressed throughout the brain reinforcement circuitry, and plays a major role in reward processing, mood control and the development of addiction. This neuromodulator system is composed of three receptors, mu, delta and kappa, interacting with a family of opioid peptides derived from POMC (β-endorphin), preproenkephalin (pEnk) and preprodynorphin (pDyn) precursors. Knockout mice targeting each gene of the opioid system have been created almost two decades ago.

RSK2 signaling in medial habenula contributes to acute morphine analgesia.

It has been established that mu opioid receptors activate the ERK1/2 signaling cascade both in vitro and in vivo. The Ser/Thr kinase RSK2 is a direct downstream effector of ERK1/2 and has a role in cellular signaling, cell survival growth, and differentiation; however, its role in biological processes in vivo is less well known. Here we determined whether RSK2 contributes to mu-mediated signaling in vivo.

Protracted abstinence from distinct drugs of abuse shows regulation of a common gene network.

Addiction is a chronic brain disorder. Prolonged abstinence from drugs of abuse involves dysphoria, high stress responsiveness and craving. The neurobiology of drug abstinence, however, is poorly understood.