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

Progress in Neuro-Psychopharmacology and Biological Psychiatry, Journal Year: 2024, Volume and Issue: 133, P. 111008 - 111008

Published: April 18, 2024

Language: Английский

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Converging Effects of Chronic Pain and Binge Alcohol Consumption on Anterior Insular Cortex Neurons Projecting to the Dorsolateral Striatum in Male Mice

Journal of Neuroscience, Journal Year: 2024, Volume and Issue: unknown, P. e1287232024 - e1287232024

Published: March 7, 2024

Chronic pain and alcohol use disorder (AUD) are highly comorbid, patients with chronic more likely to meet the criteria for AUD. Evidence suggests that both conditions alter similar brain pathways, yet this relationship remains poorly understood. Prior work shows anterior insular cortex (AIC) is involved in disorder. However, circuit-specific changes elicited by combination of remain understudied. The goal was elucidate converging effects binge consumption on AIC neurons send projections dorsolateral striatum (DLS). Here, we used Drinking-in-the-Dark (DID) paradigm model binge-like drinking mice underwent spared nerve injury (SNI), after which whole-cell patch-clamp electrophysiological recordings were performed acute slices measure intrinsic synaptic properties AIC-DLS neurons. In male, but not female mice, found SNI no prior exposure consumed less compared sham mice. Electrophysiological analyses showed from SNI-alcohol male displayed increased neuronal excitability frequency miniature excitatory postsynaptic currents. exposed amounts following SNI. Together, our data suggest interaction have a direct effect transmission onto may be critical understanding how alters motivated behaviors associated alcohol. Significant Statement We currently poor processes Commonly, consumption. indicate nerve-injury reduces Only these pain-alcohol specific population an increase excitability. can sensitize circuit could targeted attenuating intake treating alcohol-use disorders.

Language: Английский

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Peripheral alcohol metabolism dictates ethanol consumption and drinking microstructure in mice

Alcohol Clinical and Experimental Research, Journal Year: 2025, Volume and Issue: unknown

Published: March 21, 2025

Ethanol metabolism is intimately linked with the physiological and behavioral aspects of ethanol consumption. mainly oxidized by alcohol dehydrogenase (ADH) to acetaldehyde further acetate via aldehyde dehydrogenases (ALDHs). Understanding how its metabolites work together initiate drive continued consumption crucial for identifying interventions use disorder (AUD). Therefore, goal our study was determine ADH1, which peripherally expressed metabolizes >90% ingested ethanol, modulates metabolite distribution downstream behaviors. in drinking-in-the-dark (DID) two-bottle choice (2BC) drinking paradigms, concentrations, lickometry were assessed after ADH1 inhibition and/or Adh1-knockout (Adh1 KO) mice. We found that Adh1 KO mice both sexes exhibited decreased preference compared wild-type (WT) DID 2BC. inhibitor fomepizole (4-MP) also significantly normal sweetened studies. Measurement revealed increased at 1 h but not 15 min, peripheral slightly timepoints, ethanol-induced increases abolished administration controls. Similarly, accumulation as a function 2-fold higher or 4-MP-treated then used this perturbation affects microstructure. consume most their first 30 like WT mice, display altered temporal shifts behaviors do form bout structures, resulting lower Our demonstrates ADH1-mediated key determinant consumption, highlighting fundamental knowledge gap regarding

Language: Английский

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Neural activity in anterior insula at drinking onset and licking relates to compulsion-like alcohol consumption

Journal of Neuroscience, Journal Year: 2024, Volume and Issue: unknown, P. e1490232023 - e1490232023

Published: Jan. 19, 2024

Much remains unknown about the etiology of compulsion-like alcohol drinking, where consumption persists despite adverse consequences. The role anterior insula (AIC) in emotion, motivation, and interoception makes this brain region a likely candidate to drive challenge-resistant behavior, including compulsive drinking. Indeed, subcortical projections from AIC promote intake rats, are recruited heavy-drinking humans during compulsion for alcohol, highlighting importance need more information activity patterns that support aversion-resistant responding. Single-unit was recorded 15 male rats alcohol-only consumption. We found three sustained-firing phenotypes, sustained-increase, sustained-decrease, drinking-onset cells, as well several firing synchronized with licking. While many neurons had session-long changes, only increases at drinking onset greater under conditions. Further, cells persistent maintained pauses licking, suggesting roles maintaining breaks. not elevated saccharin similar lack effect inhibition on sweet fluid studies. In addition, we observed subsecond changes neural tightly entrained One lick-synched pattern (determined all licks session) predicted while separate lick-associated correlated across Collectively, these data provide integrated model important relevance how promotes sustained motivated responding generally. Significance Statement cortex is known behaviors, especially those involving challenge emotion regulation, but sustain such behaviors remain incompletely understood. Here examined related consumption, Compulsion can strongly contribute problems, also represents useful test case understanding could behavior face challenge. Insula showed patterns. Compulsion-like exhibited specific led suggestion helps evaluate condition onset, then provides plateau lick-related maintain

Language: Английский

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The impact of abstinence from chronic alcohol consumption on the mouse striatal proteome: sex and subregion-specific differences

Frontiers in Pharmacology, Journal Year: 2024, Volume and Issue: 15

Published: June 3, 2024

Alcohol misuse is the third leading preventable cause of death in world. The World Health Organization currently estimates that 1 20 deaths are directly alcohol related. One ways which consuming excessive levels can both and indirectly affect human mortality morbidity, through chronic inflammation. Recently, studies have suggested a link between increased use incidence neuroinflammatory-related diseases. However, mechanism potentially influences neuroinflammatory processes still being uncovered. We implemented an unbiased proteomics exploration alcohol-induced changes striatum, with specific emphasis on proteins related to striatum brain region critically involved progression disorder. Using mass spectrometry following voluntary self-administration mice, we show distinct protein abundances signaling pathways different subregions disrupted by exposure compared water drinking control mice. Further, mice were allowed experience abstinence from non-abstinent, overall proteome showed additional differences, suggesting responses evoked dependent history. To our surprise did not find or altered abundance associated inflammation, but rather affected neurodegeneration metabolic, cellular organization, translation, molecular transport processes. These outcomes suggest this model, neuroinflammation primary outcome controlling neurobehavioral function, these mediated striatal neuronal structure health.

Language: Английский

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Peripheral alcohol metabolism dictates ethanol consumption and drinking microstructure in mice

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 13, 2025

Abstract Background Ethanol metabolism is intimately linked with the physiological and behavioral aspects of ethanol consumption. mainly oxidized by alcohol dehydrogenase (ADH) to acetaldehyde further acetate via aldehyde dehydrogenases (ALDHs). Understanding how its metabolites work together initiate drive continued consumption crucial for identifying interventions use disorder (AUD). Therefore, goal our study was determine ADH1, which peripherally-expressed metabolizes >90% ingested ethanol, modulates metabolite distribution downstream behaviors. Methods in drinking-in-the-dark (DID) two-bottle choice (2BC) drinking paradigms, concentrations, lickometry were assessed after ADH1 inhibition and/or Adh1 -knockout ( KO) mice. Results We found that KO mice both sexes exhibited decreased preference compared wild-type (WT) DID 2BC. inhibitor fomepizole (4-MP) also significantly normal sweetened studies. Measurement revealed increased at 1h but not 15 min, peripheral slightly time points, ethanol-induced increases abolished administration controls. Similarly, accumulation as a function 2-fold higher or 4-MP treated then used this perturbation affects microstructure. consume most their first 30 min like WT display altered temporal shifts behaviors do form bout structures, resulting lower Conclusions Our demonstrates ADH1-mediated key determinant consumption, highlighting fundamental knowledge gap around

Language: Английский

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Impact of Plastic Sipper Devices on Alcohol Self-Administration in Rodents: Limitations for Long-Term Access Paradigms

Alcohol, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 1, 2025

Open source devices are becoming widely used in behavioral neuroscience. Despite their advantages cost effectiveness, modularity, and customization, measurements obtained using newly developed may not always recapitulate from existing validated equipment, potentially due to the materials manufacture. In this study, we evaluated a commonly open-source optical lickometer that delivers fluid via Hydropac® plastic valve multi-site intermittent access two-bottle choice (IA2BC) paradigm for alcohol consumption. Mice were tested with both traditional metal sippers equipped valves assess differences intake, preference, total Our findings revealed mice displayed reduced intake preference (10-20% v/v) delivered containing sippers. Notably, effect was observed at testing sites, suggesting generalizable phenomenon. The decreased also specific alcohol, as water, quinine, sucrose consumption unaffected by sipper type. To investigate underlying cause of consumption, pre-incubated 20% found pre-treated even when This suggests prolonged interaction between components alter fluid, likely generating unpalatable contaminants. These results highlight limitation long-term self-administration studies. While these remain suitable limited paradigms use extended protocols compromise data integrity. study underscores need rigorous validation hardware each research project.

Language: Английский

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A single-cell genomic atlas for the effects of chronic ethanol exposure in the mouse dorsal striatum

Molecular Psychiatry, Journal Year: 2025, Volume and Issue: unknown

Published: April 16, 2025

Language: Английский

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Identification of Novel BDNF-Specific Corticostriatal Circuitries

eNeuro, Journal Year: 2023, Volume and Issue: 10(5), P. ENEURO.0238 - 21.2023

Published: May 1, 2023

Abstract Brain-derived neurotrophic factor (BDNF) is released from axon terminals originating in the cerebral cortex onto striatal neurons. Here, we characterized BDNF neurons corticostriatal circuitry. First, used -Cre and Ribotag transgenic mouse lines to label BDNF-positive detected expression all subregions of prefrontal (PFC). Next, a retrograde viral tracing strategy, combination with knock-in mice, map cortical outputs dorsomedial dorsolateral striatum (DMS DLS, respectively). We found that BDNF- expressing located medial (mPFC) project mainly DMS, those primary secondary motor cortices (M1 M2, respectively) agranular insular (AI) DLS. In contrast, orbitofrontal (OFC) differentially target dorsal (DS) depending on their mediolateral rostrocaudal location. Specifically, DMS innervated by ventral part (MO VO, respectively), whereas DLS receives projections specifically lateral OFC (LO). Together, our study uncovers previously unknown circuitries. These findings could have important implications for role signaling pathways.

Language: Английский

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Sex-dependent, lateralized engagement of anterior insular cortex inputs to the dorsolateral striatum in binge alcohol drinking

eLife, Journal Year: 2024, Volume and Issue: 13

Published: June 28, 2024

How does alcohol consumption alter synaptic transmission across time, and do these alcohol-induced neuroadaptations occur similarly in both male female mice? Previously we identified that anterior insular cortex (AIC) projections to the dorsolateral striatum (DLS) are uniquely sensitive male, but not mice, play a role governing binge mice (Haggerty et al., 2022). Here, by using high-resolution behavior data paired with in-vivo fiber photometry, show how similar levels of intake achieved via different behavioral strategies sexes, inter-drinking session thirst states predict future intakes females, males. Furthermore, presynaptic calcium activity recorded from AIC inputs DLS 3 weeks water followed changes across, fluid, sex, brain circuit lateralization. By time-locking peri-initiation drinking events also into left robustly encode behaviors relative consumption. These findings suggest fluid-, sex-, lateralization-dependent for engagement further contextualize at DLS.

Language: Английский

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