IntelliCage: the development and perspectives of a mouse- and user-friendly automated behavioral test system

Frontiers in Behavioral Neuroscience, Journal Year: 2024, Volume and Issue: 17

Published: Jan. 3, 2024

IntelliCage for mice is a rodent home-cage equipped with four corner structures harboring symmetrical double panels operant conditioning at each of the two sides, either by reward (access to water) or aversion (non-painful stimuli: air-puffs, LED lights). Corner visits, nose-pokes and actual licks bottle-nipples are recorded individually using subcutaneously implanted transponders RFID identification up 16 adult housed in same home-cage. This allows recording individual in-cage activity applying reward/punishment schemes corners workflows designed on versatile graphic user interface. development had roots: (i) dissatisfaction standard approaches analyzing mouse behavior, including standardization reproducibility issues, (ii) response handling housing animal welfare (iii) increasing number models produced high work burden classic manual behavioral phenotyping single mice. (iv), studies transponder-chipped outdoor settings revealed clear genetic differences corresponding those observed testing laboratory. The latter observations were important social groups, because they contradicted traditional belief that animals must be tested under isolation prevent disturbance other group members. use IntelliCages reduced indeed amount remarkably, while its flexibility was proved wide range applications worldwide transcontinental parallel testing. Essentially, lines emerged: sophisticated analysis spontaneous behavior screening new models, hypothesis many fields neuroscience. Upcoming developments aim improved stimulus presentation learning videotracking interactions within IntelliCage. Its main advantages live context not stressfully handled experiments, restricted time can run absence humans, it increases worldwide, (iv) industrial cage permits retrospective data statistical tools even after years.

Language: Английский

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Self-management with alcohol over lifespan: psychological mechanisms, neurobiological underpinnings, and risk assessment

Molecular Psychiatry, Journal Year: 2023, Volume and Issue: 28(7), P. 2683 - 2696

Published: April 28, 2023

Abstract Self-management includes all behavioural measures and cognitive activities aimed at coping with challenges arising throughout the lifespan. While virtually of these can be met without pharmacological means, alcohol consumption has long been instrumentalized as a supporting tool to help problems selectively adolescence, adulthood, ageing. Here, we present, our knowledge, first systematic review instrumentalization We searched MEDLINE, Google Scholar, PsycINFO CINAHL (from Jan, 1990, Dec, 2022) analysed patterns, goals potential neurobiological mechanisms. Evidence shows regular non-addictive use self-manage developmental issues during Alcohol is used overcome from dysfunctional personality traits, which manifest in adolescence. A large range psychiatric disorders gives rise for self-management distinct symptoms starting mainly adulthood. identify those neuropharmacological effects that serve under specific conditions. Finally, discuss adverse associated risks arise self-management. Even well-controlled adversely impacts health. Based on findings, suggest implementation an entirely new view. Health policy action may actively embrace both sides phenomenon through personalized informed allows harm-controlled alcohol.

Language: Английский

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ARC/ARG3.1 binds the nuclear polyadenylate-binding protein RRM and regulates neuronal activity-dependent formation of nuclear speckles

Cell Reports, Journal Year: 2025, Volume and Issue: 44(4), P. 115525 - 115525

Published: April 1, 2025

ARC is a neuronal activity-induced protein interaction hub with critical roles in synaptic plasticity and memory. localizes to synapses the nucleus, but its nuclear functions are little known. Following vivo long-term potentiation (LTP) induction dentate gyrus, we show that accumulates nucleosol fraction interchromatin space of granule cells. Proteomic analysis immunoprecipitated complexes identifies proteins involved pre-mRNA processing. We demonstrate endogenous protein-protein polyadenylate-binding 1 (PABPN1) paraspeckles polypyrimidine tract-binding (PTB)-associated splicing factor (PSF). In vitro peptide binding arrays direct purified PABPN1 poly(A)-RNA recognition motif. 3D morphometric imaging reveals structural changes foci corresponding classical speckles following LTP. Depletion disrupts maintenance activity-dependent formation speckles, thus implicating regulation speckle dynamics

Language: Английский

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Linking drug and food addiction: an overview of the shared neural circuits and behavioral phenotype

Frontiers in Behavioral Neuroscience, Journal Year: 2023, Volume and Issue: 17

Published: Sept. 12, 2023

Despite a lack of agreement on its definition and inclusion as specific diagnosable disturbance, the food addiction construct is supported by several neurobiological behavioral clinical preclinical findings. Recognizing critical to understanding how why it manifests. In this overview, we focused those follows: 1. hyperpalatable effects in development; 2. brain regions involved both drug addiction; 3. animal models highlighting commonalities between substance use disorders addiction. Although results collected through studies emerged from protocols differing ways, they clearly highlight manifestations alterations characteristics. To develop improved models, heterogeneity should be acknowledged embraced so that research can systematically investigate role variables development different features addiction-like behavior models.

Language: Английский

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Is DNA methylation in the brain a mechanism of alcohol use disorder?

Frontiers in Behavioral Neuroscience, Journal Year: 2023, Volume and Issue: 17

Published: Jan. 26, 2023

Alcohol use disorder (AUD) is a worldwide problem. Unfortunately, the molecular mechanisms of alcohol misuse are still poorly understood, therefore successful therapeutic approaches limited. Accumulating data indicate that tendency for compulsive inherited, suggesting genetic background as an important factor. However, probability to develop AUD also affected by life experience and environmental factors. Therefore, epigenetic modifications altered over lifetime likely contribute increased risk misuse. Here, we review literature looking link between DNA methylation in brain, common modification, AUD-related behaviors humans, mice rats. We sum up main findings, identify existing gaps our knowledge future directions research.

Language: Английский

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Diverse processing of pharmacological and natural rewards by the central amygdala

Cell Reports, Journal Year: 2023, Volume and Issue: 42(9), P. 113036 - 113036

Published: Aug. 23, 2023

The central amygdala (CeA) with its medial (CeM) and lateral (CeL) nuclei is the brain hub for processing stimuli emotional context. CeL nucleus gives a strong inhibitory input to CeM, this local circuitry assigns values (positive or negative) incoming stimuli, guiding appropriate behavior (approach avoid). However, particular involvement of CeA in such emotionally relevant information adaptations are not yet well understood. In study, we examined synaptic plasticity after exposure two types rewards, pharmacological (cocaine) natural (sugar). We found that both rewards engage where they generate silent synapses resulting strengthening network. only cocaine triggers CeL, which leads weakening excitatory inputs. Finally, chemogenetic inhibition CeM attenuates animal preference sugar, while activation delays cocaine-induced increase locomotor activity.

Language: Английский

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Factors Associated with Relapses in Alcohol and Substance Use Disorder

Eurasian Journal of Medicine, Journal Year: 2024, Volume and Issue: 55(S1), P. 75 - 81

Published: Feb. 28, 2024

Alcohol and substance use disorder (ASUD) is a chronic condition featuring relapses remissions. Due to their multifactorial nature, the causes of in ASUD are not fully understood it important update information. Therefore, we aimed provide an on research examining factors associated with relapses, organized into sections. Factors such as early age onset, dysfunction brain reward system, poor physical health, sleep disturbance, comorbid psychiatric disorders, severity ASUD, craving, low self-efcacy, negative life events, socioeconomic status have been consistently shown increase relapse rate ASUD. Conversely, positive family functioning, strong social support, treatment motivation regular medication appear decrease rates. Studies gender genetic yielded mixed results no consistent relationship has found. While pharmaceutical agents methadone, buprenorphine naltrexone efective preventing opioid alcohol disorders; there proven be other disorders. Psychotherapeutic approaches, including motivational interviewing, cognitive behavioral therapy, 12-step programs contingency management demonstrated efective. The addiction substances intricate necessitates biopsychosocial interventions. However, despite all treatments, high rates indicate necessity for support rehabilitation services. In light data obtained, afecting patients can determined appropriate interventions therapeutic approaches used prevent relapses.

Language: Английский

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Neutral sphingomyelinase controls acute and chronic alcohol effects on brain activity

Neuropharmacology, Journal Year: 2024, Volume and Issue: 253, P. 109948 - 109948

Published: April 16, 2024

Alcohol consumption is a widespread phenomenon throughout the world. However, how recreational alcohol use evolves into disorder (AUD) remains poorly understood. The Smpd3 gene and its coded protein neutral sphingomyelinase (NSM) are associated with in humans alcohol-related behaviors mice, suggesting potential role this transition. Using multiparametric magnetic resonance imaging, we characterized of NSM acute chronic effects on brain anatomy function female mice. Chronic voluntary (16 vol.% for at least 6 days) affected WT reducing regional structure volume predominantly cortical regions. Attenuated activity prevented these anatomical changes. Functional MRI linked adaptations to functional changes: mice significantly modulated resting state connectivity (RS FC) response an ethanol challenge (i.p. bolus 2 g kg-1) heterozygous knockout (Fro), but not Acute administration alcohol-naïve decreased RS FC brainstem regions, key finding that was amplified Fro Regarding direct pharmacological effects, increased cerebral blood (rCBV) many areas. Here, otherwise attenuated rCBV enhanced it Altogether, findings suggest differential responses alcohol. Therefore, targeting may be useful prevention or treatment AUD.

Language: Английский

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Autophosphorylation of αCaMKII regulates alcohol consumption by controlling sedative effects of alcohol and alcohol‐induced loss of excitatory synapses

Addiction Biology, Journal Year: 2023, Volume and Issue: 28(5)

Published: April 15, 2023

Abstract Calcium/calmodulin‐dependent kinase II (CaMKII) is a key enzyme at the glutamatergic synapses. CAMK2A gene variants have been linked with alcohol use disorder (AUD) by an unknown mechanism. Here, we looked for link between αCaMKII autophosphorylation and AUD aetiology. Autophosphorylation‐deficient heterozygous mutant mice (T286A +/− ) were trained in IntelliCages to test role of activity AUD‐related behaviours. The synapses morphology CeA was studied animals drinking using 3D electron microscopy. We found that T286A mutants consumed less more sensitive sedating effects alcohol, as compared wild‐type littermates (WT). After voluntary drinking, had excitatory CeA, alcohol‐naive animals. This change correlated consumption not reversed after withdrawal observed WT mice. Our study suggests affects controlling sedative preventing synaptic loss individuals alcohol. finding advances our understanding molecular processes regulate dependence.

Language: Английский

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Nicotine, THC, and Dolutegravir Modulate E-Cigarette-Induced Changes in Addiction- and Inflammation-Associated Genes in Rat Brains and Astrocytes

Brain Sciences, Journal Year: 2023, Volume and Issue: 13(11), P. 1556 - 1556

Published: Nov. 7, 2023

E-cigarette use has been marketed as a safer alternative to traditional cigarettes, means of smoking cessation, and are used at higher rate than the general population in people with HIV (PWH). Early growth receptor 2 (EGR2) Activity-Regulated Cytoskeleton-Associated Protein (ARC) have role addiction, synaptic plasticity, inflammation, neurodegeneration. This study showed that 10 days exposure e-cigarette vapor altered gene expression brains 6-month-old, male, Sprague Dawley rats. Specifically, solvent propylene glycol (PG) downregulated EGR2 ARC mRNA frontal cortex, an effect which was reversed by nicotine (NIC) THC, suggesting PG could protective against NIC cannabis dependence. However, vitro, upregulated 18 h cultured C6 rat astrocytes may neuroinflammatory effects. PG-induced upregulation but not THC. The antiretroviral DTG had on decreasing EGR2, is concerning because implicated latency reversal, T-cell apoptosis, neuroinflammation, process underlies development HIV-associated neurocognitive disorders.

Language: Английский

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