Corticotropin-releasing factor and GABA in the ventral tegmental area modulate partner preference formation in male and female prairie voles (Microtus ochrogaster) DOI Creative Commons

Kyle R. Gossman,

Camryn Serra Lowe,

Adrianna Kirckof

et al.

Frontiers in Neuroscience, Journal Year: 2024, Volume and Issue: 18

Published: July 23, 2024

Introduction The mesolimbic reward system is associated with the promotion and rewarding benefits of social relationships. In socially monogamous prairie vole ( Microtus ochrogaster ), establishment a pair bond can be displayed by robust preference for breeding partner aggressive rejection unfamiliar conspecifics. Mesolimbic dopamine signaling influences bond-related behaviors within through transmission receptor activity in nucleus accumbens. However, only one experiment has examined how ventral tegmental area (VTA), region that produces much fore- mid-brain dopamine, regulates these behaviors. Specifically, inhibition either glutamate or GABA neurons VTA during brief courtship promoted formation male voles. heterogeneous structure contains GABA, as well receives variety projections including corticotropin-releasing factor (CRF) suggested to modulate release. Methods We used pharmacological manipulation examine CRF female we 3 h test, choice assess following an infused bicuculline 1 cohabitation muscimol CP154526, CRFR1 antagonist, 24 opposite-sex conspecific. Results Our study demonstrated bicuculline, A preference, whereas low-dose muscimol, agonist, inhibited both Conclusion This inputs into necessary

Language: Английский

Toward a Better Understanding of the Mechanisms and Pathophysiology of Anhedonia: Are We Ready for Translation? DOI
Diego A. Pizzagalli

American Journal of Psychiatry, Journal Year: 2022, Volume and Issue: 179(7), P. 458 - 469

Published: July 1, 2022

Anhedonia—the loss of pleasure or lack reactivity to pleasurable stimuli—remains a formidable treatment challenge across neuropsychiatric disorders. In major depressive disorder, anhedonia has been linked poor disease course, worse response psychological, pharmacological, and neurostimulation treatments, increased suicide risk. Moreover, although some neural abnormalities normalize after successful treatment, several persist—for example, blunted activation the ventral striatum reward-related cues reduced functional connectivity involving striatum. Critically, these have also identified in unaffected, never-depressed children parents with disorder found prospectively predict first onset depression. Thus, may be promising targets for prevention. Despite appreciation clinical importance its underlying mechanisms, important gaps remain. this overview, author summarizes extant knowledge about pathophysiology anhedonia, which provide road map toward novel prevention strategies, then highlights priorities facilitate clinically meaningful breakthroughs. These include need 1) appropriately controlled trials, especially those embracing an experimental therapeutics approach probe target engagement; 2) preclinical models relevant stronger translational value; 3) scales that incorporate neuroscientific advances our understanding anhedonia. The concludes by highlighting future directions, emphasizing integrated, collaborative, cross-species, multilevel tackling anhedonic phenotypes.

Language: Английский

Citations

107
How Microbes Affect Depression: Underlying Mechanisms via the Gut–Brain Axis and the Modulating Role of Probiotics DOI Open Access
Kazunori Suda, Kazunori Matsuda

International Journal of Molecular Sciences, Journal Year: 2022, Volume and Issue: 23(3), P. 1172 - 1172

Published: Jan. 21, 2022

Accumulating evidence suggests that the gut microbiome influences brain functions and psychological state of its host via gut–brain axis, dysbiosis has been linked to several mental illnesses, including major depressive disorder (MDD). Animal experiments have shown a depletion microbiota leads behavioral changes, is associated with pathological abnormal stress response impaired adult neurogenesis. Short-chain fatty acids such as butyrate are known contribute up-regulation brain-derived neurotrophic factor (BDNF), causes decreased levels BDNF, which could affect neuronal development synaptic plasticity. Increased permeability an influx microbial components lipopolysaccharides, resultant systemic inflammation may lead neuroinflammation in central nervous system. In light fact factors initiation exacerbation symptoms, this review summarizes current understanding molecular mechanisms involved MDD onset, discusses therapeutic potential probiotics, butyrate-producing bacteria, can mediate microbiota–gut–brain axis.

Language: Английский

Citations

82
The molecular pathophysiology of depression and the new therapeutics DOI

Haihua Tian,

Zhenyu Hu,

Jia Xu

et al.

MedComm, Journal Year: 2022, Volume and Issue: 3(3)

Published: July 21, 2022

Major depressive disorder (MDD) is a highly prevalent and disabling disorder. Despite the many hypotheses proposed to understand molecular pathophysiology of depression, it still unclear. Current treatments for depression are inadequate individuals, because limited effectiveness, delayed efficacy (usually two weeks), side effects. Consequently, novel drugs with increased speed action effectiveness required. Ketamine has shown have rapid, reliable, long-lasting antidepressant effects in treatment-resistant MDD patients represent breakthrough therapy MDD; however, concerns regarding its efficacy, potential misuse, remain. In this review, we aimed summarize mechanisms pharmacological depression. We focused on fast treatment clarified safety, tolerability, ketamine metabolites treatment, along review mechanisms, research challenges, future clinical prospects.

Language: Английский

Citations

71
Ventral tegmental area GABAergic inhibition of cholinergic interneurons in the ventral nucleus accumbens shell promotes reward reinforcement DOI
Ream Al‐Hasani, Raajaram Gowrishankar,

Gavin P. Schmitz

et al.

Nature Neuroscience, Journal Year: 2021, Volume and Issue: 24(10), P. 1414 - 1428

Published: Aug. 12, 2021

Language: Английский

Citations

91
Encore: Behavioural animal models of stress, depression and mood disorders DOI Creative Commons
Aleksa Petković, Dipesh Chaudhury

Frontiers in Behavioral Neuroscience, Journal Year: 2022, Volume and Issue: 16

Published: Aug. 8, 2022

Animal studies over the past two decades have led to extensive advances in our understanding of pathogenesis depressive and mood disorders. Among these, rodent behavioural models proved be highest informative value. Here, we present a comprehensive overview most popular with respect physiological, circuit, molecular biological correlates. Behavioural stress paradigms tests are assessed terms outcomes, strengths, weaknesses, translational value, especially domain pharmacological studies.

Language: Английский

Citations

45
Stress relief as a natural resilience mechanism against depression-like behaviors DOI Creative Commons
Yiyan Dong, Yifei Li, Xinkuan Xiang

et al.

Neuron, Journal Year: 2023, Volume and Issue: 111(23), P. 3789 - 3801.e6

Published: Sept. 29, 2023

Relief, the appetitive state after termination of aversive stimuli, is evolutionarily conserved. Understanding behavioral role this well-conserved phenomenon and its underlying neurobiological mechanisms are open important questions. Here, we discover that magnitude relief from physical stress strongly correlates with individual resilience to depression-like behaviors in chronic stressed mice. Notably, blocking causes vulnerability behaviors, whereas natural rewards supplied shortly promotes resilience. Stress mediated by reward-related mesolimbic dopamine neurons, which show minute-long, persistent activation termination. Circuitry-wise, or inhibition circuits downstream ventral tegmental area during transient period bi-directionally regulates depression These results reveal an evolutionary function identify neural substrate mediating effect. Importantly, our data suggest a strategy augmenting positive valence prevent depression.

Language: Английский

Citations

27
Exploring causal mechanisms of psychosis risk DOI Creative Commons
Dominic Oliver, Edward Chesney, Alexis E. Cullen

et al.

Neuroscience & Biobehavioral Reviews, Journal Year: 2024, Volume and Issue: 162, P. 105699 - 105699

Published: May 6, 2024

Robust epidemiological evidence of risk and protective factors for psychosis is essential to inform preventive interventions. Previous syntheses have classified these according their strength association with psychosis. In this critical review we appraise the distinct overlapping mechanisms 25 key environmental psychosis, link mechanistic pathways that may contribute neurochemical alterations hypothesised underlie psychotic symptoms. We then discuss implications our findings future research, specifically considering interactions between factors, exploring universal subgroup-specific improving understanding temporality dynamics, standardising operationalisation measurement developing interventions targeting factors.

Language: Английский

Citations

9
The nucleus accumbens in reward and aversion processing: insights and implications DOI Creative Commons
Ying Xu, Yingjie Lin, Ming Yu

et al.

Frontiers in Behavioral Neuroscience, Journal Year: 2024, Volume and Issue: 18

Published: Aug. 9, 2024

The nucleus accumbens (NAc), a central component of the brain's reward circuitry, has been implicated in wide range behaviors and emotional states. Emerging evidence, primarily drawing from recent rodent studies, suggests that function NAc aversion processing is multifaceted. Prolonged stress or drug use induces maladaptive neuronal which results pathological conditions. This review aims to provide comprehensive up-to-date insights on role motivated behavior regulation highlights areas demand further in-depth analysis. It synthesizes latest findings how distinct populations pathways contribute opposite valences. examines neuromodulators, especially monoamines, influence NAc's control over various motivational Furthermore, it delves into complex underlying mechanisms psychiatric disorders such as addiction depression evaluates prospective interventions restore functionality.

Language: Английский

Citations

9
An inhibitory brainstem input to dopamine neurons encodes nicotine aversion DOI Creative Commons
Christine Liu, Amanda J. Tose, Jeroen P. H. Verharen

et al.

Neuron, Journal Year: 2022, Volume and Issue: 110(18), P. 3018 - 3035.e7

Published: Aug. 2, 2022

Language: Английский

Citations

33
Stress to inflammation and anhedonia: Mechanistic insights from preclinical and clinical models DOI Creative Commons
Chloe C. Boyle, Julienne E. Bower, Naomi I. Eisenberger

et al.

Neuroscience & Biobehavioral Reviews, Journal Year: 2023, Volume and Issue: 152, P. 105307 - 105307

Published: July 6, 2023

Language: Английский

Citations

18