Distinct Chrna5 mutations link excessive alcohol use to types I/II vulnerability profiles and IPN GABAergic neurons.

Genome wide association and animal studies have implicated genetic variations in CHRNΑ5, encoding the α5 subunit-containing nicotinic acetylcholine receptors (α5*nAChRs), as a risk factor for developing alcohol use disorders (AUDs). To understand how α5*nAChR mutations may influence alcohol (EtOH) drinking behavior, we used a two-bottle choice procedure with intermittent access to alcohol in male and female transgenic mice expressing either the highly frequent human single nucleotide polymorphism (α5SNP/rs16969968) or a deletion of the Chrna5 gene (α5KO). AUDs-related preconsommatory traits (anxiety, sensation-seeking and impulsivity) were assessed with a battery of relevant tasks (elevated-plus maze, novel place preference and step-down inhibitory avoidance).

Acute stress differently modulates interneurons excitability and synaptic plasticity in the primary motor cortex of wild-type and SOD1 mouse model of ALS.

Primary motor cortex (M1) network stability depends on activity of inhibitory interneurons, for which susceptibility to stress was previously demonstrated in limbic regions. Hyperexcitability in M1 following changes in the excitatory/inhibitory balance is a key pathological hallmark of amyotrophic lateral sclerosis (ALS). Using electrophysiological approaches, we assessed the impact of acute restraint stress on inhibitory interneurons excitability and global synaptic plasticity in M1 of the SOD1 ALS mouse model at a late pre-symptomatic stage (10-12.

Chronic alcohol-induced long-lasting working memory deficits are associated with altered histone H3K9 dimethylation in the prefrontal cortex.

Introduction: Epigenetic modifications have emerged as key contributors to the enduring behavioral, molecular and epigenetic neuroadaptations during withdrawal from chronic alcohol exposure. The present study investigated the long-term consequences of chronic alcohol exposure on spatial working memory (WM) and associated changes of transcriptionally repressive histone H3 lysine 9 dimethylation (H3K9me) in the prefrontal cortex (PFC).

Methods: Male C57BL/6 mice were allowed free access to either 12% (v/v) ethanol for 5 months followed by a 3-week abstinence period or water.

Chronic alcohol consumption shifts learning strategies and synaptic plasticity from hippocampus to striatum-dependent pathways.

Introduction: The hippocampus and striatum have dissociable roles in memory and are necessary for spatial and procedural/cued learning, respectively. Emotionally charged, stressful events promote the use of striatal- over hippocampus-dependent learning through the activation of the amygdala. An emerging hypothesis suggests that chronic consumption of addictive drugs similarly disrupt spatial/declarative memory while facilitating striatum-dependent associative learning.

Preventive Effects of Baclofen but Not Diazepam on Hippocampal Memory and Glucocorticoid Alterations After Prolonged Alcohol Withdrawal in Mice.

Our study aims at comparing in C57/Bl male mice, the impact of repeated injections of baclofen (an agonist of GABAB receptor) or diazepam (a benzodiazepine acting through a positive allosteric modulation of GABAA receptor) administered during the alcohol-withdrawal period on hippocampus-dependent memory impairments and brain regional glucocorticoid dysfunction after a short (1-week) or a long (4-week) abstinence. Hence, mice were submitted to a 6-month alcohol consumption (12%v/v) and were progressively withdrawn to water. Then, after a 1- or 4-weeks abstinence, they were submitted to a contextual memory task followed by measurements of corticosterone concentrations in the dorsal hippocampus (dHPC), the ventral hippocampus (vHPC) and the prefrontal cortex (PFC).

Sustained corticosterone rise in the prefrontal cortex is a key factor for chronic stress-induced working memory deficits in mice.

Exposure to prolonged, unpredictable stress leads to glucocorticoids-mediated long-lasting neuroendocrine abnormalities associated with emotional and cognitive impairments. Excessive levels of serum glucocorticoids (cortisol in humans, corticosterone in rodents) contribute notably to deficits in working memory (WM), a task which heavily relies on functional interactions between the medial prefrontal cortex (PFC) and the dorsal hippocampus (dHPC). However, it is unknown whether stress-induced increases in plasma corticosterone mirror corticosterone levels in specific brain regions critical for WM.

Baclofen but Not Diazepam Alleviates Alcohol-Seeking Behavior and Hypothalamic-Pituitary-Adrenal Axis Dysfunction in Stressed Withdrawn Mice.

This study compares the impact of repeated injections of baclofen (an agonist of GABA receptors) or diazepam (a benzodiazepine having an agonist action on GABA receptors) given during the alcohol-withdrawal period on the stress-induced restoration of alcohol-seeking behavior and hypothalamic-pituitary-adrenal (HPA) axis dysfunction after a long (4 weeks) abstinence. Thus, C57BL/6 mice were submitted to a 6-month alcohol consumption [12% volume/volume (v/v)] and were progressively withdrawn to water before testing. Diazepam (Valium, Roche) and baclofen (Baclofen, Mylan) were administered intraperitoneally for 15 consecutive days (1 injection/day) during the withdrawal period at decreasing doses ranging from 1.

The Synergistic Enhancing-Memory Effect of Donepezil and S 38093 (a Histamine H Antagonist) Is Mediated by Increased Neural Activity in the Septo-hippocampal Circuitry in Middle-Aged Mice.

Donepezil, an acetylcholinesterase inhibitor, induces only moderate symptomatic effects on memory in Alzheimer's disease patients. An alternative strategy for treatment of cognitive symptoms could be to act simultaneously on both histaminergic and cholinergic pathways, to create a synergistic effect. To that aim, 14 month old C57/Bl6 mice were administered per oesophagy during nine consecutive days with Donepezil (at 0.

Roles of Hippocampal Somatostatin Receptor Subtypes in Stress Response and Emotionality.

Altered brain somatostatin functions recently appeared as key elements for the pathogenesis of stress-related neuropsychiatric disorders. The hippocampus exerts an inhibitory feedback on stress but the mechanisms involved remain unclear. We investigated herein the role of hippocampal somatostatin receptor subtypes in both stress response and behavioral emotionality using C57BL/6, wild type and sst or sst knockout mice.

Behavioral effects of chronic stress in the Fmr1 mouse model for fragile X syndrome.

Fragile X Syndrome (FXS) is a pervasive developmental disorder due to a mutation in the FMR1 X-linked gene. Despite its clear genetic cause, the expression of FXS symptoms is known to be modulated by environmental factors, including stress. Furthermore, several studies have shown disturbances in stress regulatory systems in FXS patients and Fmr1 mice.

Alcohol withdrawal induces long-lasting spatial working memory impairments: relationship with changes in corticosterone response in the prefrontal cortex.

This study intends to determine whether long-lasting glucocorticoids (GCs) dysregulation in the prefrontal cortex (PFC) or the dorsal hippocampus (dHPC) play a causal role in the maintenance of working memory (WM) deficits observed after alcohol withdrawal. Here, we report that C57/BL6 male mice submitted to 6 months alcohol consumption (12 percent v/v) followed by 1 (1W) or 6 weeks (6W) withdrawal periods exhibit WM deficits in a spatial alternation task and an exaggerated corticosterone rise during and after memory testing in the PFC but not the dHPC. In contrast, emotional reactivity evaluated in a plus-maze is altered only in the 1W group.

Acute stress blocks the caffeine-induced enhancement of contextual memory retrieval in mice.

This study investigated in mice the dose-effect of caffeine on memory retrieval in non-stress and stress conditions. C57 Bl/6 Jico mice learned two consecutive discriminations (D1 and D2) in a four-hole board which involved either distinct contextual (CSD) or similar contextual (SSD) cues. All mice received an i.

Stress induced a shift from dorsal hippocampus to prefrontal cortex dependent memory retrieval: role of regional corticosterone.

Most of the deleterious effects of stress on memory retrieval are due to a dysfunction of the hippocampo-prefrontal cortex interplay. The role of the stress-induced regional corticosterone increase in such dysfunction remains however unclear, since there is no published study as yet dedicated to measuring corticosterone concentrations simultaneously in both the prefrontal cortex (mPFC) and the hippocampus (dHPC) in relation with memory impairments. To that aim, we first showed in Experiment 1 that an acute stress (3 electric footschocks; 0.

Retinoic acid modulates intrahippocampal levels of corticosterone in middle-aged mice: consequences on hippocampal plasticity and contextual memory.

It is now established that vitamin A and its derivatives, retinoic acid (RA), are required for cognitive functions in adulthood. RA hyposignaling and hyperactivity of glucocorticoid (GC) pathway appear concomitantly during aging and would contribute to the deterioration of hippocampal synaptic plasticity and functions. Furthermore, recent data have evidenced counteracting effects of retinoids on GC signaling pathway.