Chronic alcohol consumption alters home‐cage behaviors and responses to ethologically relevant predator tasks in mice

Alcoholism Clinical and Experimental Research, Journal Year: 2022, Volume and Issue: 46(8), P. 1616 - 1629

Published: July 7, 2022

Abstract Background Alcohol withdrawal is a key component of severe alcohol use disorder. Animal models tend to focus on traditional anxiety/stress tests. While these have been essential advancing our understanding the biology withdrawal, abrupt cessation drinking following heavy consumption can also trigger withdrawal‐related affective states that impact responses variety life events and stressors. To this end, we show behaviors in tasks differ task demand intensity are altered during male female mice after voluntary access. Methods Male miceunderwent six weeks intermittent two‐bottle choice exposure followed by behavioral The tests included—Home cage: low‐stress baseline environment measure spontaneous natural behaviors; Open field: anxiety‐inducing bright novel environment; Looming disc: arena with protective hut where exposed series discs mimic an overhead predator, Robogator‐simulated predator task: forced foraging presence robot “attacks” when near food pellet large open arena. Results A history impacted sex‐dependent manner. In home cage, induced reductions digging heightened stress coping through increase grooming time. males, increased rearing yielded greater vigilance/exploration familiar environment. open‐field test revealed anxiety phenotype both alcohol. showed no alterations looming disc task, while females escape than water controls, indicative active stress‐response behaviors. Robogator hesitant/avoidant alcohol‐exposed under demands. Conclusions Few drugs robust evidence efficacy clinical trials for withdrawal. Understanding how alters males linked misuse aid developing better medications treating individuals AUD.

Language: Английский

---

Sensitivity and Resilience to Predator Stress-Enhanced Ethanol Drinking Is Associated With Sex-Dependent Differences in Stress-Regulating Systems

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

Published: May 11, 2022

Stress can increase ethanol drinking, and evidence confirms an association between post-traumatic stress disorder (PTSD) the development of alcohol use (AUD). Exposure to predator odor is considered a traumatic stressor, (PS) has been used extensively as animal model PTSD. Our prior work determined that repeated exposure intermittent PS significantly increased anxiety-related behavior, corticosterone levels, neuronal activation in hippocampus prefrontal cortex naïve male female C57BL/6J mice. Intermittent also subsequent drinking subgroup animals, with heterogeneity responses seen comorbid PTSD AUD. The present studies built upon this began characterize “sensitivity” “resilience” PS-enhanced drinking. Ethanol was measured during baseline, exposure, post-stress; mice were euthanized after 24-h abstinence. Calculation median interquartile ranges identified “sensitive” (>20% over baseline) “resilient” (no change or decrease from subgroups. intake 24% (↑60%) 20% (↑71%) subgroup. Plasma levels both sexes, but lower vs. In representative subgroups, analyzed by Western Blotting for corticotropin releasing factor (CRF) receptor 1, CRF 2, binding protein, glucocorticoid receptor, separate age-matched cortex, higher only females. hippocampus, 2 across sexes. These results indicate sex strongly influences effects on proteins regulating anxiety responses. They further suggest targeting system receptors AUD needs consider comorbidity treated individuals.

Language: Английский

---

Mouse parasubthalamic Crh neurons drive alcohol drinking escalation and behavioral disinhibition

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: July 10, 2024

Abstract Corticotropin-releasing factor (CRF, encoded by Crh ) signaling is thought to play a critical role in the development of excessive alcohol drinking and emotional physical pain associated with withdrawal. Here, we investigated parasubthalamic nucleus (PSTN) as potential source CRF relevant control consumption, affect, nociception mice. We identified PSTN neurons neuronal subpopulation that exerts potent unique influence on behavior promoting not only but also saccharin drinking, while are otherwise known suppress consummatory behaviors. Furthermore, causally implicated escalation intake produced chronic intermittent ethanol (CIE) vapor inhalation, mouse model use disorder. In contrast our predictions, ability increase mediated 1 signaling. Moreover, pattern behavioral disinhibition reduced driven their activation does support negative reinforcement motivational basis for concomitant drinking. Finally, silencing expression slowed down mice exposed CIE accelerated recovery from withdrawal-induced mechanical hyperalgesia. Altogether, results suggest may represent an important node brain circuitry linking disorder sweet liking novelty seeking.

Language: Английский

---

Impact of Elevated Brain IL-6 in Transgenic Mice on the Behavioral and Neurochemical Consequences of Chronic Alcohol Exposure

Cells, Journal Year: 2023, Volume and Issue: 12(18), P. 2306 - 2306

Published: Sept. 19, 2023

Alcohol consumption activates the neuroimmune system of brain, a in which brain astrocytes and microglia play dominant roles. These glial cells normally produce low levels factors, are important signaling factors regulators function. activation is known to dysregulate production such as cytokine IL-6, thereby changing status could impact actions alcohol. The consequences neuroimmune-alcohol interactions not fully known. In current studies we investigated this issue transgenic (TG) mice with altered relative IL-6. TG express elevated astrocyte-produced condition occur alcohol exposure. Standard behavioral tests drinking negative affect/emotionality were carried out homozygous heterozygous control assess on chronic intermittent (ethanol) (CIE) exposure these behaviors. expressions signal transduction synaptic proteins also assessed by Western blot identify alcohol-neuroimmune neurochemistry. results from show that respect IL-6 significantly impacts effects multiple levels.

Language: Английский

---

Areas of Convergence and Divergence in Adolescent Social Isolation and Binge Drinking: A Review

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

Published: March 30, 2022

Adolescence is a critical developmental period characterized by enhanced social interactions, ongoing development of the frontal cortex and maturation synaptic connections throughout brain. Adolescents spend more time interacting with peers than any other age group display heightened reward sensitivity, impulsivity diminished inhibitory self-control, which contribute to increased risky behaviors, including initiation progression alcohol use. Compared adults, adolescents are less susceptible negative effects ethanol, but stress, particularly stress. Juvenile exposure isolation or binge ethanol disrupts connections, dendritic spine morphology, myelin remodeling in cortex. These structural may underlie behavioral cognitive deficits seen later life, memory deficits, anxiety-like behavior risk for use disorders (AUD). Although stress fields actively investigating mechanisms through these occur, significant gaps our understanding exist, intersection two fields. This review will highlight areas convergence divergence adolescent exposure. We focus on how can impact lead lasting changes adulthood. call attention need mechanistic studies inclusion evaluation sex differences molecular, structural, responses.

Language: Английский

---

Chronic MAP4343 reverses escalated alcohol drinking in a mouse model of alcohol use disorder

Neuropsychopharmacology, Journal Year: 2023, Volume and Issue: unknown

Published: Jan. 20, 2023

Abstract Alcohol use disorders can be driven by negative reinforcement. Alterations of the microtubule cytoskeleton have been associated with mood regulation in context depression. Notably, MAP4343, a pregnenolone derivative known to promote tubulin assembly, has antidepressant properties. In present study, we tested hypothesis that MAP4343 may reduce excessive alcohol drinking mouse model dependence normalizing affect during withdrawal. Adult male C57BL/6J mice were given limited access voluntary and ethanol intake escalation was induced chronic intermittent (CIE) vapor inhalation. Chronic, but not acute, administration reduced this effect more pronounced CIE-exposed mice. There complex interaction between effects on affective behaviors. elevated plus maze, tended increase open-arm exploration alcohol-naive it alcohol-withdrawn tail suspension test, immobility selectively Air-exposed alcohol-drinking Finally, countered plasma corticosterone reduction CIE. Parallel analysis post-translational modifications revealed lower α-tubulin acetylation medial prefrontal cortex CIE-withdrawn Altogether, these data support relevance microtubules as therapeutic target for treatment AUD.

Language: Английский

---

Adolescent intermittent alcohol exposure produces strain-specific cross-sensitization to nicotine and other behavioral adaptations in adulthood in C57BL/6J and DBA/2J mice

Pharmacology Biochemistry and Behavior, Journal Year: 2023, Volume and Issue: 232, P. 173655 - 173655

Published: Oct. 5, 2023

Language: Английский

---

Influence of early‐life adversity on responses to acute and chronic ethanol in female mice

Alcohol Clinical and Experimental Research, Journal Year: 2022, Volume and Issue: 47(2), P. 336 - 347

Published: Dec. 4, 2022

Abstract Background Stressful early‐life experiences increase the risk of developing an alcohol use disorder. We previously found that male C57BL/6J mice reared under limited bedding and nesting (LBN) conditions, a model adversity, escalate their ethanol intake in limited‐access two‐bottle choice (2BC) sessions faster than control (CTL)‐reared counterparts when exposed to chronic intermittent (CIE) vapor inhalation. However, consumption female littermates was not affected by LBN or CIE. In present study, we sought determine whether this phenotype reflected general insensitivity influence stress on responses. Methods first experiment, CTL females with history 2BC combined CIE were tested affective nociceptive assays during withdrawal. second group females, examined ethanol‐induced antinociception, sedation, plasma clearance, c‐Fos induction. Results withdrawn from 2BC, increased digging, reduced grooming, immobility tail suspension test regardless history. contrast, rearing lowered mechanical thresholds exposure. acutely treated ethanol, facilitated antinociception delayed onset sedation without influencing clearance rate induction paraventricular nucleus hypothalamus, thalamus, central amygdala, auditory cortex. Conclusion withdrawal produced multiple indices negative affect suggesting motivation consume may differ air‐exposed despite equivalent intake. Contrasted our previous findings males, LBN‐induced hyperalgesia drinkers specific females. Lower sensitivity acute antinociceptive effect contribute reinforcing but are sufficient

Language: Английский

---

Ethanol combined with energy drinks: Two decades of research in rodents

Frontiers in Behavioral Neuroscience, Journal Year: 2023, Volume and Issue: 16

Published: March 2, 2023

Many studies raised concerns on alcoholic beverages consumption mixed with energy drinks (AmED), which can induce higher rates of binge drinking and earlier development alcohol use disorders. After 20 years research, few laboratory animals have focused the effects this mixture neurobiological pharmacological mechanisms underlying them. We found 16 articles AmED administration to rodents evaluating its voluntary consumption, locomotion, anxiety-like behavior, memory, influence onset time seizures, biochemical neurochemical measures. Some these indicated (ED) alter pattern motivation consume ethanol (EtOH); increase expression sensitization EtOH stimulant effect proportion sensitized mice; decrease aversiveness high concentrations EtOH, among other effects. In addition hastens loss righting reflex memory are controversial. acute no difference was in blood concentration (BEC) received or without ED, but after 60 days treatment, group had lower BEC levels than group. Data parameters not consistent. Although presented glucose when drugs were administered by gavage , observed a self-administration protocol. may kidney damage, plasma urea, uric acid creatinine compared EtOH. Chronic causes an inflammatory response oxidative stress, cell death cortex hypothalamus adult rats. These controversial results show that diverse depend sex, age lineage animals, duration treatment route administration. Further research is necessary evaluate biological

Language: Английский

---

Septo-hypothalamic regulation of binge-like alcohol consumption by the nociceptin system

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: March 16, 2024

ABSTRACT High intensity alcohol drinking during binge episodes overwhelmingly contributes to the socioeconomic burden created by Alcohol Use Disorders (AUD). Novel interventions are needed add current therapeutic toolkit and nociceptin receptor (NOP) antagonists have shown promise in reducing heavy days patients with an AUD. However, endogenous locus of peptide discrete sites NOP action underlying this effect remains understudied. Here we show that lateral septum (LS), a region contributing drinking, is enriched neurons expressing mRNA coding for ( Pnoc) . Pnoc-expressing LS (LS Pnoc ) tuned stimuli associated negative valence display increased excitability withdrawal from binge-like drinking. activation was found aversive qualities also potentiates behavior, suggesting convergence circuitry promotes aversion drives consumption. Viral mediated tracing functional assessment projection fields revealed GABAergic synapses locally within LS, downstream hypothalamus (LH) supramammillary nucleus (SuM). Genetic deletion attenuated intake male mice while LH SuM decrease females. Together, these findings first demonstrate population nociceptin-expressing consumption identifies sex-dependent modulation NOP.

Language: Английский

---