Dynamic regulation of CeA gene expression during acute and protracted abstinence from chronic binge drinking of male and female C57BL/6J mice.

While there are numerous brain regions that have been shown to play a role in this AUD in humans and animal models, the central nucleus of the amygdala (CeA) has emerged as a critically important locus mediating binge alcohol consumption. In this study, we sought to understand how relative gene expression of key signaling molecules in the CeA changes during different periods of abstinence following bouts of binge drinking. To test this, we performed drinking in the dark (DID) on two separate cohorts of C57BL/6J mice and collected CeA brain tissue at 1 day (acute) and 7 days (protracted) abstinence after DID.

Increased reactivity of the paraventricular nucleus of the hypothalamus and decreased threat responding in male rats following psilocin administration.

Psychedelics have experienced renewed interest following positive clinical effects, however the neurobiological mechanisms underlying effects remain unclear. The paraventricular nucleus of the hypothalamus (PVN) plays an integral role in stress response, autonomic function, social behavior, and other affective processes. We investigated the effect of psilocin, the psychoactive metabolite of psilocybin, on PVN reactivity in Sprague Dawley rats.

Prospective associations of behavioral economic demand for cannabis and alcohol with simultaneous cannabis and alcohol use among young adults.

Behavioral economic demand for cannabis and alcohol is robustly associated with cannabis use and alcohol use, respectively. However, few studies have examined the contributions of cannabis and alcohol demand to simultaneous cannabis and alcohol use, which is common among young adults. We examined prospective associations of cannabis demand and alcohol demand with propensity for simultaneous use (broadly defined as using both cannabis and alcohol in the same day) and with cannabis and alcohol consumption during simultaneous use days among young adults.

Sex differences in basal motivated behavior, chronic ethanol drinking, and amygdala activity in female and male mice.

Alcohol use disorder (AUD) is a major public health concern that despite its prevalence, lacks a widely-effective treatment due to the complexity of AUD pathology. AUD is highly comorbid with other psychiatric conditions including anxiety and mood disorders, however it is unclear how these disorders influence each other. The underlying etiology of these comorbidities is difficult to decipher and factors including sex, stress, and the environment further complicate both diagnosis and treatment strategies.

Adolescent alcohol exposure persistently alters orbitofrontal cortical encoding of Pavlovian conditional stimulus components in female rats.

Exposure to alcohol during adolescence impacts cortical and limbic brain regions undergoing maturation. In rodent models, long-term effects on behavior and neurophysiology have been described after adolescent intermittent ethanol (AIE), especially in males. We hypothesized that AIE in female rats increases conditional approach to a reward-predictive cue and corresponding neuronal activity in the orbitofrontal cortex (OFC) and nucleus accumbens (NAc).

Neuroactive Steroids, Toll-like Receptors, and Neuroimmune Regulation: Insights into Their Impact on Neuropsychiatric Disorders.

Pregnane neuroactive steroids, notably allopregnanolone and pregnenolone, exhibit efficacy in mitigating inflammatory signals triggered by toll-like receptor (TLR) activation, thus attenuating the production of inflammatory factors. Clinical studies highlight their therapeutic potential, particularly in conditions like postpartum depression (PPD), where the FDA-approved compound brexanolone, an intravenous formulation of allopregnanolone, effectively suppresses TLR-mediated inflammatory pathways, predicting symptom improvement. Additionally, pregnane neurosteroids exhibit trophic and anti-inflammatory properties, stimulating the production of vital trophic proteins and anti-inflammatory factors.

Chronic alcohol consumption alters sex-dependent BNST neuron function in rhesus macaques.

Repeated alcohol drinking contributes to a number of neuropsychiatric diseases, including alcohol use disorder and co-expressed anxiety and mood disorders. Women are more susceptible to the development and expression of these diseases with the same history of alcohol exposure as men, suggesting they may be more sensitive to alcohol-induced plasticity in limbic brain regions controlling alcohol drinking, stress responsivity, and reward processing, among other behaviors. Using a translational model of alcohol drinking in rhesus monkeys, we examined sex differences in the basal function and plasticity of neurons in the bed nucleus of the stria terminalis (BNST), a brain region in the extended amygdala shown to be a hub circuit node dysregulated in individuals with anxiety and alcohol use disorder.

From learned value to sustained bias: how reward conditioning changes attentional priority.

Introduction: Attentional bias to reward-associated stimuli can occur even when it interferes with goal-driven behavior. One theory posits that dopaminergic signaling in the striatum during reward conditioning leads to changes in visual cortical and parietal representations of the stimulus used, and this, in turn, sustains attentional bias even when reward is discontinued. However, only a few studies have examined neural activity during both rewarded and unrewarded task phases.

Chronic alcohol consumption alters sex-dependent BNST neuron function in rhesus macaques.

Repeated alcohol drinking contributes to a number of neuropsychiatric diseases, including alcohol use disorder and co-expressed anxiety and mood disorders. Women are more susceptible to the development and expression of these diseases with the same history of alcohol exposure as men, suggesting they may be more sensitive to alcohol-induced plasticity in limbic brain regions controlling alcohol drinking, stress responsivity, and reward processing, among other behaviors. Using a translational model of alcohol drinking in rhesus monkeys, we examined sex differences in the basal function and plasticity of neurons in the bed nucleus of the stria terminalis (BNST), a brain region in the extended amygdala shown to be a hub circuit node dysregulated in individuals with anxiety and alcohol use disorder.

β-arrestin-biased Allosteric Modulator of Neurotensin Receptor 1 Reduces Ethanol Drinking and Responses to Ethanol Administration in Rodents.

Alcohol use disorders (AUDs) impose an enormous societal and financial burden, and world-wide, alcohol misuse is the 7 leading cause of premature death. Despite this, there are currently only 3 FDA approved pharmacological treatments for the treatment of AUDs in the United States. The neurotensin (Nts) system has long been implicated in modulating behaviors associated with alcohol misuse.

Inhibiting CRF Projections from the Central Amygdala to Lateral Hypothalamus and Amygdala Deletion of CRF Alters Binge-Like Ethanol Drinking in a Sex-Dependent Manner.

Background: Binge alcohol drinking is a dangerous pattern of consumption that can contribute to the development of more severe alcohol use disorders (AUDs). Importantly, the rate and severity of AUDs has historically differed between men and women, suggesting that there may be sex differences in the central mechanisms that modulate alcohol (ethanol) consumption. Corticotropin releasing factor (CRF) is a centrally expressed neuropeptide that has been implicated in the modulation of binge-like ethanol intake, and emerging data highlight sex differences in central CRF systems.

CD20/MS4A1 is a mammalian olfactory receptor expressed in a subset of olfactory sensory neurons that mediates innate avoidance of predators.

The mammalian olfactory system detects and discriminates between millions of odorants to elicit appropriate behavioral responses. While much has been learned about how olfactory sensory neurons detect odorants and signal their presence, how specific innate, unlearned behaviors are initiated in response to ethologically relevant odors remains poorly understood. Here, we show that the 4-transmembrane protein CD20, also known as MS4A1, is expressed in a previously uncharacterized subpopulation of olfactory sensory neurons in the main olfactory epithelium of the murine nasal cavity and functions as a mammalian olfactory receptor that recognizes compounds produced by mouse predators.

Predator odor stress reactivity, alcohol drinking and the endocannabinoid system.

Post-traumatic stress disorder (PTSD) and alcohol use disorder (AUD) are highly comorbid and individual differences in response to stress suggest resilient and susceptible populations. Using animal models to target neurobiological mechanisms associated with individual variability in stress coping responses and the relationship with subsequent increases in alcohol consumption has important implications for the field of traumatic stress and alcohol disorders. The current review discusses the unique advantages of utilizing predator odor stressor exposure models, specifically using 2,5-dihydro-2,4,5-trimethylthiazoline (TMT) on better understanding PTSD pathophysiology and neurobiological mechanisms associated with stress reactivity and subsequent increases in alcohol drinking.

mGlu and mGlu receptor negative allosteric modulators attenuate the interoceptive effects of alcohol in male and female rats.

Rationale: The subjective effects of alcohol are associated with alcohol use disorder (AUD) vulnerability and treatment outcomes. The interoceptive effects of alcohol are part of these subjective effects and can be measured in animal models using drug discrimination procedures. The newly developed mGlu and mGlu negative allosteric modulators (NAMs) are potential therapeutics for AUD and may alter interoceptive sensitivity to alcohol.

Daily and Momentary Associations Between Gender Minority Stress and Resilience With Alcohol Outcomes.

Background And Purpose: Minority stressors have been linked with alcohol use among transgender and gender diverse (TGD); however, no ecological momentary assessment studies have examined daily links between minority stress and alcohol use specifically among TGD. This study examined gender minority stressors and resilience as predictors of same-day or momentary alcohol-related outcomes. Feasibility and acceptability of procedures were evaluated.

Interactive effects of alcohol and cannabis quantities in the prediction of same-day negative consequences among young adults.

Background: Simultaneous alcohol and cannabis use is common, but observational studies examining negative consequences of simultaneous use have rarely considered dose-related interactions between alcohol and cannabis. This study examined interactions between quantities of cannabis and alcohol consumed in predicting negative consequences on simultaneous use days.

Methods: Young adults (N = 151; 64% female; 62% White) reporting recent simultaneous use and at least weekly alcohol and cannabis use completed 21 daily, smartphone-based surveys assessing previous day quantities of cannabis and alcohol used, types of cannabis used (flower, concentrates, edibles), and negative substance-related consequences.

Retrieval of an ethanol-conditioned taste aversion promotes GABAergic plasticity in the insular cortex.

Blunted sensitivity to ethanol's aversive effects can increase motivation to consume ethanol; yet, the neurobiological circuits responsible for encoding these aversive properties are not fully understood. Plasticity in cells projecting from the insular cortex (IC) to the basolateral amygdala (BLA) is critical for taste aversion learning and retrieval, suggesting this circuit's potential involvement in modulating the aversive properties of ethanol. Here, we tested the hypothesis that GABAergic activity onto IC-BLA projections would be facilitated following the retrieval of an ethanol-conditioned taste aversion (CTA).

Epigenetic regulation of microglia and neurons by proinflammatory signaling following adolescent intermittent ethanol (AIE) exposure and in human AUD.

Adolescent alcohol drinking is linked to high rates of adult alcohol problems and alcohol use disorder (AUD). The Neurobiology of Alcohol Drinking in Adulthood (NADIA) consortium adolescent intermittent ethanol (AIE) models adolescent binge drinking, followed by abstinent maturation to adulthood to determine the persistent AIE changes in neurobiology and behavior. AIE increases adult alcohol drinking and preference, increases anxiety and reward seeking, and disrupts sleep and cognition, all risks for AUD.

The impact of prenatal alcohol, synthetic cannabinoid and co-exposure on behavioral adaptations in adolescent offspring and alcohol self-administration in adulthood.

Prenatal exposure to alcohol or cannabinoids can produce enduring neurobiological, cognitive, and behavioral changes in the offspring. Furthermore, prenatal co-exposure to alcohol and cannabinoids induces malformations in brain regions associated with reward and stress-related circuitry. This study examined the effects of co-exposure to alcohol and the synthetic cannabinoid (SCB) CP55,940 throughout gastrulation and neurulation in rats on basal corticosterone levels and a battery of behavioral tests during adolescence and alcohol self-administration in adulthood.

Perceptions, Experiences, and Patterns of Cannabis Use in Individuals with Mood and Anxiety Disorders in the Context of Cannabis Legalization and Medical Cannabis Program in Canada - A Qualitative Study.

Introduction: Perceptions of cannabis as a potential medical treatment for mood and anxiety disorders have been increasing in the context of legalizations, availability, and medical cannabis programs, though current evidence predominately indicates risks and negative effects of cannabis use (CU) on mental health outcomes. This study aims to understand motivations, perceptions, effects, and patterns of CU in individuals with mood and anxiety disorders.

Methods: Thirty-six adult patients diagnosed with mood or anxiety disorders, obsessive-compulsive disorder, or posttraumatic stress disorder who were currently using cannabis completed an in-depth qualitative interview on individual motivations, perceptions, experiences, effects, and patterns of their CU.

A role for circuitry of the cortical amygdala in excessive alcohol drinking, withdrawal, and alcohol use disorder.

Alcohol use disorder (AUD) poses a significant public health challenge. Individuals with AUD engage in chronic and excessive alcohol consumption, leading to cycles of intoxication, withdrawal, and craving behaviors. This review explores the involvement of the cortical amygdala (CoA), a cortical brain region that has primarily been examined in relation to olfactory behavior, in the expression of alcohol dependence and excessive alcohol drinking.

The role of brain serotonin signaling in excessive alcohol consumption and withdrawal: A call for more research in females.

Alcohol Use Disorder (AUD) is a leading cause of death and disability worldwide, but current treatments are insufficient in fully addressing the symptoms that often lead to relapses in alcohol consumption. The brain's serotonin system has been implicated in AUD for decades and is a major regulator of stress-related behaviors associated with increased alcohol consumption. This review will discuss the current literature on the association between neurobiological adaptations in serotonin systems and AUD in humans as well as the effectiveness of serotonin receptor manipulations on alcohol-related behaviors like consumption and withdrawal.

Acute and chronic alcohol modulation of extended amygdala calcium dynamics.

The central amygdala (CeA) and bed nucleus of the stria terminalis (BNST) are reciprocally connected nodes of the extended amygdala thought to play an important role in alcohol consumption. Studies of immediate-early genes indicate that BNST and CeA are acutely activated following alcohol drinking and may signal alcohol reward in nondependent drinkers, while stress signaling in the extended amygdala following chronic alcohol exposure drives increased drinking via negative reinforcement. However, the temporal dynamics of neuronal activation in these regions during drinking behavior are poorly understood.

GABA release from central amygdala neurotensin neurons differentially modulates ethanol consumption in male and female mice.

The central nucleus of the amygdala is known to play key roles in alcohol use and affect. Neurotensin neurons in the central nucleus of the amygdala have been shown to regulate alcohol drinking in male mice. However, little is known about which neurotransmitters released by these cells drive alcohol consumption or whether these cells drive alcohol consumption in female mice.