mesolimbic

INTRODUCTION: Food addiction (FA) is highly prevalent among people with obesity (PwO) and may constitute a key factor in weight loss failure or weight regain. GLP-1 analogues have been shown to act on the mesolimbic system, which is related to hedonic overeating and substance abuse. We aimed to study the effects of low doses of semaglutide on FA symptomatology and to evaluate whether the presence of FA have a negative impact on weight loss despite treatment with semaglutide. METHODS: One hundred and thirteen PwO (45...

INTRODUCTION: In the dopamine system, the mesolimbic pathway, including the dorsal striatum, underlies the reinforcing properties of tobacco smoking, and the mesocortical pathway, including the dorsolateral prefrontal cortex (dlPFC), is critical for cognitive functioning. Dysregulated dopamine signaling has been linked to drug-seeking behaviors and cognitbie deficits. The dorsal striatum and dlPFC are structurally and functionally connected and are the key regions for cognitive functioning...

The Nociceptin/Orphanin FQ (N/OFQ) peptide and its receptor NOP are highly expressed within several regions of the mesolimbic system, including the ventral tegmental area (VTA). Evidence indicates that the N/OFQ-NOP receptor system is involved in reward processing and historically it has been proposed that activation of NOP receptors attenuates the motivation for substances of abuse. However, recent findings demonstrated that drug self-administration and relapse to drug-seeking are also attenuated after administration of NOP receptor antagonists...

Major depressive disorder (MDD) is characterized by diverse debilitating symptoms that include loss of motivation and anhedonia. If multiple medications, psychotherapy, and electroconvulsive therapy fail in some patients with MDD, their condition is then termed treatment-resistant depression (TRD). MDD can be associated with abnormalities in the reward-system-dopaminergic mesolimbic pathway, in which the nucleus accumbens (NAc) and ventral tegmental area (VTA) play major roles. Deep brain stimulation (DBS) applied to the NAc alleviates the depressive symptoms of MDD...

Cholecystokinin (CCK) is a neuropeptide modulating digestion, glucose levels, neurotransmitters and memory. Recent studies suggest that CCK exhibits neuroprotective effects in Alzheimer's disease (AD) and Parkinson's disease (PD). Thus, we review the physiological function and therapeutic potential of CCK. The neuropeptide facilitates hippocampal glutamate release and gates GABAergic basket cell activity, which improves declarative memory acquisition, but inhibits consolidation. Cortical CCK alters recognition memory and enhances audio-visual processing...

In rodents, orexin neuropeptides regulate motivation and reward-seeking via orexin 1 receptor (OX1R) signaling in the mesolimbic dopaminergic system. This role is clearly established for rewards inherent to drugs of abuse but less so for natural rewards. Reported effects of the selective OX1R antagonist (SO1RA) SB-334867 on motivation for palatable food are ambiguous. In our experimental conditions neither SB-334867, nor two additional, structurally different SO1RAs, ACT-335827 and the clinical development candidate nivasorexant, affected effort-based responding for sucrose in rats...

Reciprocal communication between the gut microbiota and the brain, commonly referred to as the "gut-brain-axis" is crucial in maintaining overall physiological homeostasis. Gut microbiota development and brain maturation (neuronal connectivity and plasticity) appear to be synchronized and to follow the same timeline during childhood (immature), adolescence (expansion) and adulthood (completion). It is important to note that the mesolimbic reward circuitry develops early on, whereas the maturation of the inhibitory frontal cortical neurons is delayed...

OBJECTIVE: Auditory verbal hallucinations (AVHs) in schizophrenia is proved to be associated with dysfunction of mesolimbic-cortical circuits, especially during abnormal salient and internal verbal resource monitoring processing procedures. However, the information flow among areas involved in coordinated interaction implicated the pathophysiology of AVHs remains unclear. METHODS: We used spectral dynamic causal modeling (DCM) to quantify connections among eight critical hubs of reward network in 86 first-episode drug-naïve schizophrenia patients with AVHs (AVH), 93 patients without AVHs (NAVH), and 88 matched normal controls (NC) using resting-state functional magnetic resonance imaging...

The mesolimbic dopamine system is a crucial component of reward and reinforcement processing, including the psychotropic effects of drugs of abuse such as cocaine. Drugs of abuse can activate intracellular signaling cascades that engender long-term molecular changes to brain reward circuitry, which can promote further drug use. However, gaps remain about how the activity of these signaling pathways, such as ERK1/2 signaling, can affect cocaine-induced neurochemical plasticity and cocaine-associated behaviors specifically within dopaminergic cells...

The hippocampus is pivotal in integrating emotional processing, learning, memory, and reward-related behaviors. The dorsal hippocampus (dHPC) is particularly crucial for episodic, spatial, and associative memory, and has been shown to be necessary for context- and cue-associated reward behaviors. The nucleus accumbens (NAc), a central structure in the mesolimbic reward pathway, integrates the salience of aversive and rewarding stimuli. Despite extensive research on dHPC→NAc direct projections, their sufficiency in driving reinforcement and reward-related behavior remains to be determined...

Machine learning research has achieved large performance gains on a wide range of tasks by expanding the learning target from mean rewards to entire probability distributions of rewards - an approach known as distributional reinforcement learning (RL) 1 . The mesolimbic dopamine system is thought to underlie RL in the mammalian brain by updating a representation of mean value in the striatum 2,3 , but little is known about whether, where, and how neurons in this circuit encode information about higher-order moments of reward distributions 4 ...

Cognitive impairment is a debilitating feature of psychiatric disorders including schizophrenia, mood disorders and substance use disorders for which there is a substantial lack of effective therapies. d-Govadine (d-GOV) is a tetrahydroprotoberberine recently shown to significantly enhance working memory and behavioural flexibility in several prefrontal cortex (PFC)-dependent rodent tasks. d-GOV potentiates dopamine (DA) efflux in the mPFC and not the nucleus accumbens, a unique pharmacology that sets it apart from many dopaminergic drugs and likely contributes to its effects on cognitive function...

The medial habenula (MHb) has been identified as the limiting factor for nicotine intake and facilitating nicotine withdrawal. However, few studies have assessed MHb neuronal excitability in response to nicotine and, currently, a gap in knowledge is present for finding behavioral correlates to neuronal excitability in the region. Moreover, no study to date has evaluated sex or nicotine dosage as factors of excitability in the MHb. Here, we utilized an e-vape® self-administration (EVSA) model to determine differences between sexes with different nicotine dosages ± menthol...

Depression and anxiety are associated with dysfunction of the mesolimbic dopamine system. The rostromedial tegmental nucleus (RMTg) is predominantly composed of GABAergic neurons that exhibit dense projections and strongly inhibit mesolimbic dopaminergic neurons, proposed as a major "brake" for the system. Consequently, the RMTg may be a crucial brain region for regulating these emotions. The central cholinergic system, particularly the muscarinic receptors, plays an important regulatory role in depression and anxiety...

Tuberoinfundibular dopamine (TIDA) neurons have cell bodies located in the arcuate nucleus of the mediobasal hypothalamus. They project to the external zone of the median eminence, and the dopamine (DA) released there is carried by the hypophysial portal vasculature to the anterior pituitary. The DA then activates D2 receptors to inhibit prolactin (PRL) secretion from lactotrophs. The TIDA neuronal population is the principal regulatory factor controlling PRL secretion. The neuroendocrine role subserved by TIDA neurons sets them apart from other dopaminergic populations like the nigrostriatal and mesolimbic DA neurons...

Chronic pain is primarily conceptualized as a disease in its own right when it is associated with emotional distress and functional impairment. Pathophysiologically, dysfunction of the cortico-mesolimbic connectome is of major importance, with overlapping signals in the nociceptive and stress systems. The endocannabinoid system plays an important role in the central processing of nociceptive signals and regulates the central stress response. Clinically, there is moderate evidence that cannabis-based medicines (CBM) can contribute to a significant reduction in pain, especially the associated pain effect, and improvement in physical function and sleep quality in a proportion of patients with chronic pain...

BACKGROUND: Chronic postsurgical pain (CPP) markedly impairs patients' quality of life. Research has shown that chronic stress may extend incisional nociception in male mice. Dopaminergic (DAergic) neurons in the ventral tegmental area (VTA) are integral to stress-related mental disorders (including major depressive disorder, anxiety disorders, and PTSD) and pain. However, the impact of chronic social defeat stress (CSDS) on mesolimbic dopamine (DA) transmission in the development of CPP is yet to be established...

Increases in drug consumption over time, also known as escalation, is a key behavioral component of substance use disorder (SUD) that is related to potential harm to users, such as overdose. Studying escalation also allows researchers to investigate the transition from casual drug use to more SUD-like drug use. Understanding the neurobiological systems that drive this transition will inform therapeutic treatments in the aim to prevent increases in drug use and the development of SUD. The kappa opioid receptor (KOR) system is typically known for its role in negative affect, which is commonly found in SUD as well...

Opioids are generally known to promote hedonic food consumption. Although much of the existing evidence is primarily based on studies of the mesolimbic pathway, endogenous opioids and their receptors are widely expressed in hypothalamic appetite circuits as well; however, their role in homeostatic feeding remains unclear. Using a fluorescent opioid sensor, deltaLight, here we report that mediobasal hypothalamic opioid levels increase by feeding, which directly and indirectly inhibits agouti-related protein (AgRP)-expressing neurons through the μ-opioid receptor (MOR)...

Listening to music is an enjoyable behaviour that engages multiple networks of brain regions. As such, the act of music listening may offer a way to interrogate network activity, and to examine the reconfigurations of brain networks that have been observed in healthy aging. The present study is an exploratory examination of brain network dynamics during music listening in healthy older and younger adults. Network measures were extracted and analyzed together with behavioural data using a combination of hidden Markov modelling and partial least squares...