Glucagon-like peptide1 receptor (GLP-1R) agonists have been found to reduce alcohol drinking in rodents and overweight patients with use disorder (AUD). However, the probability of low semaglutide doses, an agonist higher potency affinity for GLP-1R, attenuate alcohol-related responses underlying neuronal mechanisms is unknown.In intermittent access model, we examined ability decrease intake block relapse-like drinking, as well imaging binding fluorescently marked nucleus accumbens (NAc)...

The orexigenic peptide ghrelin increases the release of dopamine in nucleus accumbens (NAc) shell via central receptors, especially those located ventral tegmental area (VTA). activity VTA neurons projecting to NAc shell, involves somatodendritic within VTA. However, effects on concomitant and is unknown. It further unknown whether addictive drugs, such as alcohol amphetamine, enhance levels both these areas receptor dependent mechanisms. Thus, a antagonist, JMV2959, ability i) ii) systemic...

The gut-brain peptide ghrelin and its receptor are established as a regulator of hunger reward-processing. However, the recently recognized inverse agonist, liver-expressed antimicrobial 2 (LEAP2), is less characterized. present study aimed to elucidate LEAP2s central effect on reward-related behaviors through feeding mechanism. LEAP2 was administrated centrally in mice effectively reduced intake palatable foods. Strikingly, correlated preference food. Further, rewarding memory high foods,...

While aggression is an adaptive behavior mostly triggered by competition for resources, it can also in and of itself be rewarding. Based on the common notion that female rats are not aggressive, much research has been centered around males, leading to a gap understanding neurobiology. Therefore, we asked whether intact virgin experience reward from aggressive interaction assessed seeking both sexes. To validate involvement signaling, measured mesolimbic dopamine turnover determined necessity...

The transition to alcohol use disorder (AUD) involves persistent neuroadaptations in executive control functions primarily regulated by the medial prefrontal cortex. However, neurophysiological correlates behavioral manifestations of AUD are not fully defined. association between cortical and addiction was studied using a multi-symptomatic operant model based on DSM-5 diagnostic criteria for AUD. This aimed characterize an AUD-vulnerable AUD-resistant subpopulation outbred male Wistar rats...

Objective Rats were exposed to free‐choice diets (fat plus one of two different sugar solutions, glucose or sucrose), and the metabolic consequences impact on locomotor activity anxiety‐like behavior explored. Methods For 3 weeks, 7‐week‐old male rats offered either chow only high‐fat differing in their added sugar: no sugar, sucrose, glucose. In a second experiment, after 2 weeks diets, switched from high sucrose for additional weeks. Metabolic end points included body weight, food intake,...

Abstract The mechanisms contributing to alcohol use disorder (AUD) are complex and the orexigenic peptide ghrelin, which enhances reward, is implied as a crucial modulator. major proportion of circulating ghrelin however non-octanoylated form des-acyl (DAG), whose role in reward processes unknown. As recent studies show that DAG decreases food intake, we hypothesize attenuates alcohol-related responses animal models. Acute repeated treatment dose-dependently decreased drinking male female...

The “hunger” hormone, ghrelin, is powerfully orexigenic. Even in the absence of hunger, ghrelin delivery to rats increases consumption chow, as well palatable foods, and motivated behaviour for food rewards. Inspired by finding that selection chow offered a choice diet (lard, sucrose or chow) even bingeing on high‐fat diet, we aimed explore whether effects motivation extend regular chow. Rats were conditioned lever press either pellets progressive ratio ( PR ) operant conditioning task....

The physiological effects of glucagon-like peptide-1 (GLP-1) are mainly centered on its ability to decrease blood glucose levels and facilitate satiety. Additional functions have been identified by means GLP-1 agonists such as exenatide (exendin-4; Ex4). In particular, Ex4 reduces the intake natural artificial rewards, that some extent involve activation receptors in nucleus tractus solitarius (NTS). Although acts brain, neurochemical mechanisms underlying this not fully elucidated....

Objective The lateral parabrachial nucleus (lPBN) in the brainstem has emerged as a key area involved feeding control that is targeted by several circulating anorexigenic hormones. Here, objective was to determine whether lPBN also relevant site for orexigenic hormone ghrelin, inspired studies mice and rats showing there an abundance of ghrelin receptors this area. Methods This study first explored iPBN cells respond involving Fos mapping electrophysiological rats. Next, were injected...

The behavioural responses to nicotine involve appetite-regulatory hormones; however, the effects of anorexigenic hormone amylin on reward-related behaviours induced by remain be established. Previous studies have shown that amylinergic pathway regulates alcohol, amphetamine and cocaine. Here, we evaluated salmon calcitonin (sCT), an receptor (CTR) agonist, nicotine-induced locomotor stimulation sensitisation as well dopamine release in nucleus accumbens (NAc) shell. Moreover, investigated...

Abstract The gut-brain peptide ghrelin and its receptor (GHSR) are established as a regulator of hunger reward-processing. However, the recently recognized GHSR inverse agonist, liver-expressed antimicrobial 2 (LEAP2), is less characterized. Given role in many central processes, particular reward, understanding effects LEAP2 high interest to understand reward-related behaviors disorders, including hedonic feeding eating disorders. present study aimed elucidate LEAP2s effect on through...

The glucagon-like peptide 1 receptor (GLP-1R) has recently emerged as a viable candidate target to treat alcohol use disorder (AUD) its agonists have previously shown prevent alcohol-related responses in rodents and reduce drinking overweight patients with AUD. Here, the long-acting GLP-1R agonist semaglutide was investigated on ability relapse both male female rats. Given that alcohol-induced reward driven by dopamine release nucleus accumbens (NAc) influences drinking, hypothesis inhibits...

Abstract Objective: Combining different pharmaceuticals may be beneficial when treating disorders with complex neurobiology, including alcohol use disorder (AUD). The gut-brain peptides amylin and GLP-1 of potential interest as they individually reduce intake in rodents. While the combination receptor (AMYR) glucagon-like peptide-1 (GLP-1R) agonists have been found to decrease feeding body weight obese male rats synergistically, their combined impact on is unknown. Methods: Therefore, effect...

<title>Abstract</title> The underlying neurobiology of alcohol use disorder (AUD) is complex and needs further unraveling, with one the key mechanisms being gut-brain peptide ghrelin its receptor (GHSR). However, additional substrates pathway, such as liver-expressed antimicrobial 2 (LEAP2), an endogenous GHSR inverse agonist, may contribute to this neurobiological framework. While LEAP2 modulates feeding reward through central mechanisms, effects on responses are unknown. aim present study...

Background and Purpose The limited effectiveness of current pharmacological treatments for alcohol use disorder (AUD) highlights the need novel therapies. These may involve glucagon‐like peptide‐1 receptor or amylin receptor, as treatment with agonists targeting either these receptors lowers intake. complexity mechanisms underlying AUD indicates that combining agents could enhance efficacy. While a combination GLP‐1 reduced food intake body weight synergistic‐like, its influence on is...