Chronic ethanol induces a pro-inflammatory switch in interleukin-1β regulation of GABAergic signaling in the medial prefrontal cortex of male mice

Brain Behavior and Immunity, Год журнала: 2023, Номер 110, С. 125 - 139

Опубликована: Фев. 28, 2023

Язык: Английский

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Chemogenetic inhibition of central amygdala CRF-expressing neurons decreases alcohol intake but not trauma-related behaviors in a rat model of post-traumatic stress and alcohol use disorder

Molecular Psychiatry, Год журнала: 2024, Номер 29(9), С. 2611 - 2621

Опубликована: Март 21, 2024

Post-traumatic stress disorder (PTSD) and alcohol use (AUD) are often comorbid. Few treatments exist to reduce comorbid PTSD/AUD. Elucidating the mechanisms underlying their comorbidity could reveal new avenues for therapy. Here, we employed a model of PTSD/AUD, in which rats were subjected stressful shock familiar context followed by drinking. We then examined fear overgeneralization irritability these rats. Familiar elevated drinking, increased overgeneralization, alcohol-related aggressive signs, peripheral hormones. transcripts stress- fear-relevant genes central amygdala (CeA), locus that regulates stress-mediated Compared with unstressed rats, stressed exhibited increases CeA Crh Fkbp5 decreases Bdnf Il18. Levels Nr3c1 mRNA, encodes glucocorticoid receptor, males but decreased females. Transcripts Il18 binding protein (Il18bp), Glp-1r, associated calcitonin gene-related peptide signaling (Calca, Ramp1, Crlr-1, Iapp) unaltered. Crh, not Crhr1, mRNA was stress; thus, tested whether inhibiting neurons express corticotropin-releasing factor (CRF) suppress PTSD/AUD-like behaviors. used Crh-Cre had received Cre-dependent vector encoding hM4D(Gi), an inhibitory Designer Receptors Exclusively Activated Drugs. Chemogenetic inhibition CRF reduced intake or irritability-like Our findings suggest modulates PTSD/AUD comorbidity, neural activity is primarily reducing drinking trauma-related behaviors

Язык: Английский

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Chronic alcohol induced mechanical allodynia by promoting neuroinflammation: A mouse model of alcohol‐evoked neuropathic pain

British Journal of Pharmacology, Год журнала: 2023, Номер 180(18), С. 2377 - 2392

Опубликована: Апрель 13, 2023

Abstract Background and Purpose Chronic pain is considered a key factor contributing to alcohol use disorder (AUD). The mechanisms responsible for chronic associated with consumption are unknown. We evaluated the development of in mouse model dependence investigate role neuroinflammation. Experimental Approach chronic‐intermittent ethanol two‐bottle choice CIE‐2BC paradigm generates three groups: alcohol‐dependent escalating intake, nondependent (moderate drinking) alcohol‐naïve control male female mice. measured mechanical allodynia during withdrawal after last voluntary drinking. Immunoblotting was used evaluate protein levels IBA‐1, CSFR, IL‐6, p38 ERK2/1 spinal cord tissue dependent non‐dependent animals. Key Results found significant escalation drinking group compared group. developed 72 h withdrawal, which completely reversed observed an increased hypersensitivity naïve 50% Increased IBA‐1 CSFR expression both hypersensitivity‐abstinence related neuropathy‐alcohol mice, IL‐6 ERK1/2 activation mice hypersensitivity‐related abstinence, but not alcohol‐evoked neuropathic pain. Conclusions Implications induces two distinct conditions specific type exposure: abstinence‐related about half

Язык: Английский

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Sex- and estrous-related response patterns for alcohol depend critically on the level of compulsion-like challenge

Progress in Neuro-Psychopharmacology and Biological Psychiatry, Год журнала: 2024, Номер 133, С. 111008 - 111008

Опубликована: Апрель 18, 2024

Язык: Английский

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Alcohol Dependence Induces CRF Sensitivity in Female Central Amygdala GABA Synapses

International Journal of Molecular Sciences, Год журнала: 2022, Номер 23(14), С. 7842 - 7842

Опубликована: Июль 16, 2022

Alcohol use disorder (AUD) is a chronically relapsing disease characterized by loss of control in seeking and consuming alcohol (ethanol) driven the recruitment brain stress systems. However, AUD differs among sexes: men are more likely to develop AUD, but women progress from casual binge drinking heavy quickly. The central amygdala (CeA) hub anxiety, with corticotropin-releasing factor (CRF)-CRF1 receptor Gamma-Aminobutyric Acid (GABA)-ergic signaling dysregulation occurring alcohol-dependent male rodents. we recently showed that GABAergic synapses female rats less sensitive acute effects ethanol. Here, used patch-clamp electrophysiology examine dependence on CRF modulation rat CeA transmission both sexes. We found naïve were unresponsive application compared males, although induced similar responsivity In situ hybridization revealed females had fewer neurons containing mRNA for CRF1 (Crhr1) than dependence, percentage Crhr1-expressing increased, unlike males. Overall, our data provide evidence sexually dimorphic system dependence.

Язык: Английский

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IL-18 Signaling in the Rat Central Amygdala Is Disrupted in a Comorbid Model of Post-Traumatic Stress and Alcohol Use Disorder

Cells, Год журнала: 2023, Номер 12(15), С. 1943 - 1943

Опубликована: Июль 27, 2023

Alcohol use disorder (AUD) and anxiety disorders are frequently comorbid share dysregulated neuroimmune-related pathways. Here, we used our established rat model of post-traumatic stress (PTSD)/AUD to characterize the interleukin 18 (IL-18) system in central amygdala (CeA). Male female rats underwent novel (NOV) familiar (FAM) shock stress, or no (unstressed controls; CTL) followed by voluntary alcohol drinking PTSD-related behaviors, then all received renewed access prior experiments. In situ hybridization revealed that number CeA positive cells for Il18 mRNA increased, while Il18bp decreased both male FAM stressed versus CTL. No changes were observed Il18r1 expression across groups. Ex vivo electrophysiology showed IL-18 reduced GABAA-mediated miniature inhibitory postsynaptic currents (mIPSCs) frequencies CTL, suggesting GABA release, regardless sex. Notably, this presynaptic effect was lost NOV males, it persisted females. mIPSC amplitude CTL rats, effects. Overall, results suggest with impacts IL-18-system and, sex-related fashion, IL-18's modulatory function at synapses.

Язык: Английский

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Chronic ethanol alters adrenergic receptor gene expression and produces cognitive deficits in male mice

Neurobiology of Stress, Год журнала: 2023, Номер 24, С. 100542 - 100542

Опубликована: Апрель 28, 2023

Hyperkateifia and stress-induced alcohol cravings drive relapse in individuals with use disorder (AUD). The brain stress signal norepinephrine (also known as noradrenaline) tightly controls cognitive affective behavior was thought to be broadly dysregulated AUD. locus coeruleus (LC) is a major source of forebrain norepinephrine, it recently discovered that the LC sends distinct projections addiction-associated regions suggesting alcohol-induced noradrenergic changes may more region-specific than originally thought. Here we investigated whether ethanol dependence alters adrenergic receptor gene expression medial prefrontal cortex (mPFC) central amgydala (CeA), these mediate impairment negative state withdrawal. We exposed male C57BL/6J mice chronic intermittent vapor-2 bottle choice paradigm (CIE-2BC) induce dependence, assessed reference memory, anxiety-like transcript levels during 3-6 days Dependence bidirectionally altered mouse α1 β mRNA levels, potentially leading reduced mPFC signaling enhanced influence over CeA. These were accompanied by long-term retention deficits shift search strategy modified Barnes maze task, well greater spontaneous digging hyponeophagia. Current clinical studies are evaluating compounds treatment for AUD-associated hyperkatefia, our findings can contribute refinement therapies increasing understanding specific neural systems symptoms targeted.

Язык: Английский

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Salidroside ameliorates memory impairment following long-term ethanol intake in rats by modulating the altered intestinal microbiota content and hippocampal gene expression

Frontiers in Microbiology, Год журнала: 2023, Номер 14

Опубликована: Июнь 9, 2023

Salidroside (Sal), the main component of a famous herb Rhodiola rosea L, enhances memory performance and reduces fatigue. Therefore, this study assessed effect Sal on impairment induced by long-term intake ethanol (EtOH) in rats investigated its relevant mechanisms using gut microbiota metagenomic analysis hippocampal transcriptomic analysis.Eighteen male SD were divided into normal control group (CON group), EtOH model (Model treatment (Sal group). The Model groups intragastrically (i.g.) received 2 g/kg for 30 consecutive days, whereas CON was given an equal volume distilled water. Meanwhile, administered i.g. mg/kg 60 min after intake. All tested eight-arm maze their function every 3 days. On 30th day, analyses hippocampus performed.Compared with group, reduced total time to complete task, decreased number arm entries, abated working error that significant from 9th day. Additionally, intervention improved composition, such as increased abundance Actinobacteria Bifidobacterium, which related metabolism amino acids terpenoid carbohydrate, endocrine function, signal transduction neurotransmitters. In hippocampus, differentially expressed 68 genes (54 increased, 14 decreased), compared affected these changes: 15 11 decreased. And, enrichment revealed structural components ribosome, mRNA splicing process, protein translation, mitochondria immunological reaction. Finally, correlation found positively correlated abnormal upregulation Tomm7 but negatively Alistipes_indistinctus, Lactobacillus_taiwanensis, Lactobacillus_paragasseri, Lactobacillus johnsonii.Sal caused rats, may be regulation dysbiosis dysfunction.

Язык: Английский

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Neurobiology of Stress-Induced Nicotine Relapse

International Journal of Molecular Sciences, Год журнала: 2024, Номер 25(3), С. 1482 - 1482

Опубликована: Янв. 25, 2024

Tobacco smoking is the leading cause of preventable death and disease. Although there are some FAD-approved medicines for controlling smoking, relapse rate remains very high. Among factors that could induce nicotine relapse, stress might be most important one. In last decades, preclinical studies have generated many new findings lead to a better understanding stress-induced nicotine-seeking. Several molecules such as α3β4 nicotinic acetylcholine receptor, α2-adrenergic receptors, cannabinoid receptor 1, trace amine-associated neuropeptide systems (corticotropin-releasing factor its dynorphine kappa opioid receptor) been linked relapse. this review, we discuss recent advances in neurobiology, treatment targets, potential therapeutics We also may influence should considered future studies. final section, perspective on research directions provided. Further investigation neurobiology will shed light development help us understand interactions between reward brain.

Язык: Английский

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Noradrenaline modulates central amygdala GABA transmission and alcohol drinking in female rats

Biological Psychiatry, Год журнала: 2025, Номер unknown

Опубликована: Апрель 1, 2025

Alcohol use disorder (AUD) is a chronic relapsing and leading preventable cause of death worldwide. The central nucleus the amygdala (CeA) hub for stress AUD. Noradrenaline (norepinephrine; NE) regulates brain's response to alcohol. We previously reported that α1 adrenergic receptors drive moderate alcohol intake, while β contribute excessive drinking associated with dependence in male rats. Here, we determined withdrawal alter CeA noradrenergic system female rats using ex vivo electrophysiology, situ hybridization, site-specific behavioral pharmacology, RNA-sequencing data from postmortem samples obtained donors without NE bidirectionally (increase decrease) modulated GABAergic transmission via both receptors. Prazosin, an receptor antagonist, reduced intake non-dependent dependent females, propranolol, only females. While produced partial functional recovery modulation CeA, some cellular patterns mRNA expression persist. Although did not observe any differences gene our human AUD donors, found downregulation ADRA1A basolateral dorsolateral prefrontal cortex, compared controls. Amygdalar are key neural substrates Our results support ongoing development receptor-specific medication highlight promising efficacy

Язык: Английский

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