Sex-specific effects of psychedelic drug exposure on central amygdala reactivity and behavioral responding.

Psilocybin and its active metabolite psilocin have been shown to elicit rapid and long-lasting symptom improvements in a variety of affective psychiatric illnesses. However, the region-specific alterations underlying these therapeutic effects remain relatively unknown. The central amygdala (CeA) is a primary output region within the extended amygdala that is dysregulated in affective psychiatric disorders.

Activation of hypothalamic-enhanced adult-born neurons restores cognitive and affective function in Alzheimer's disease.

Patients with Alzheimer's disease (AD) exhibit progressive memory loss, depression, and anxiety, accompanied by impaired adult hippocampal neurogenesis (AHN). Whether AHN can be enhanced in impaired AD brain to restore cognitive and affective function remains elusive. Here, we report that patterned optogenetic stimulation of the hypothalamic supramammillary nucleus (SuM) enhances AHN in two distinct AD mouse models, 5×FAD and 3×Tg-AD.

Subcortical serotonin 5HT receptor-containing neurons sex-specifically regulate binge-like alcohol consumption, social, and arousal behaviors in mice.

Binge alcohol consumption induces discrete social and arousal disturbances in human populations that promote increased drinking and accelerate the progression of Alcohol Use Disorder. Here, we show in a mouse model that binge alcohol consumption disrupts social recognition in females and potentiates sensorimotor arousal in males. These negative behavioral outcomes were associated with sex-specific adaptations in serotonergic signaling systems within the lateral habenula (LHb) and the bed nucleus of the stria terminalis (BNST), particularly those related to the receptor 5HT.

Association Between Fatty Acid Amide Hydrolase and Alcohol Response Phenotypes: A Positron Emission Tomography Imaging Study With [C]CURB in Heavy-Drinking Youth.

Background: Reductions in fatty acid amide hydrolase (FAAH), the catabolic enzyme for the endocannabinoid anandamide, may play a role in drinking behavior and risk for alcohol use disorder. We tested the hypotheses that lower brain FAAH levels in heavy-drinking youth are related to increased alcohol intake, hazardous drinking, and differential response to alcohol.

Methods: FAAH levels in the striatum, prefrontal cortex, and whole brain were determined using positron emission tomography imaging of [C]CURB in heavy-drinking youth (N = 31; 19-25 years of age).

Indomethacin restores loss of hippocampal neurogenesis and cholinergic innervation and reduces innate immune expression and reversal learning deficits in adult male and female rats following adolescent ethanol exposure.

Background: Adolescent intermittent ethanol (AIE) exposure causes long-term changes in the brain and behavior of adult male rodents, including persistent induction of innate immune pathways, reductions in hippocampal neurogenic and forebrain cholinergic neuronal markers, and reversal learning deficits. The current study tests the hypothesis that proinflammatory induction mediates AIE-induced (1) loss of adult neurogenesis (i.e.

Targeting Persistent Changes in Neuroimmune and Epigenetic Signaling in Adolescent Drinking to Treat Alcohol Use Disorder in Adulthood.

Studies universally find early age of drinking onset is linked to lifelong risks of alcohol problems and alcohol use disorder (AUD). Assessment of the lasting effect of drinking during adolescent development in humans is confounded by the diversity of environmental and genetic factors that affect adolescent development, including emerging personality disorders and progressive increases in drinking trajectories into adulthood. Preclinical studies using an adolescent intermittent ethanol (AIE) exposure rat model of underage binge drinking avoid the human confounds and support lifelong changes that increase risks.

The outcome of boosting mitochondrial activity in alcohol-associated liver disease is organ-dependent.

Background And Aims: Alcohol-associated liver disease (ALD) accounts for 70% of liver-related deaths in Europe, with no effective approved therapies. Although mitochondrial dysfunction is one of the earliest manifestations of alcohol-induced injury, restoring mitochondrial activity remains a problematic strategy due to oxidative stress. Here, we identify methylation-controlled J protein (MCJ) as a mediator for ALD progression and hypothesize that targeting MCJ may help in recovering mitochondrial fitness without collateral oxidative damage.

Alcohol Dependence Modifies Brain Networks Activated During Withdrawal and Reaccess: A c-Fos-Based Analysis in Mice.

Background: High-level alcohol consumption causes neuroplastic changes in the brain that promote pathological drinking behavior. Some of these changes have been characterized in defined brain circuits and cell types, but unbiased approaches are needed to explore broader patterns of adaptations.

Methods: We used whole-brain c-Fos mapping and network analysis to assess patterns of neuronal activity during alcohol withdrawal and following reaccess in a well-characterized model of alcohol dependence.

Sex moderates family history of alcohol use disorder and childhood maltreatment effects on an fMRI stop-signal task.

Childhood maltreatment (CM) and a family history (FH) of alcohol use disorder (AUD) are each associated with increased impulsivity. However, their unique or shared brain targets remain unknown. Furthermore, both CM and FH demonstrate sex-dependent effects on brain and behavior.

Pharmacological administration of 3α,5α-THP into the nucleus accumbens core increases 3α,5α-THP expression and reduces alcohol self-administration.

Background: Alcohol affects multiple circuits in the brain, mainly disrupting the delicate balance between inhibitory γ-aminobutyric acid (GABA) transmission and excitatory glutamate signaling in brain areas involved in reward circuits. These include the amygdala, nucleus accumbens (Acb), and ventral tegmental area (VTA). This action impairs circuits that regulate behavioral control of craving and alcohol seeking and intake.

Astrocyte expression in the extended amygdala of C57BL/6J mice is sex-dependently affected by chronic intermittent and binge-like ethanol exposure.

Excessive ethanol drinking is a major problem within the United States, causing alterations in brain plasticity and neurocognitive function. Astrocytes are glial cells that regulate neurosynaptic plasticity, modulate neurochemicals, and monitor other homeostatic roles. Astrocytes have been found to play a part in modulating excessive ethanol consumption.

Chronic Ethanol Exposure Modulates Periaqueductal Gray to Extended Amygdala Dopamine Circuit.

The bed nucleus of the stria terminalis (BNST) is a component of the extended amygdala that regulates motivated behavior and affective states and plays an integral role in the development of alcohol-use disorder (AUD). The dorsal subdivision of the BNST (dBNST) receives dense dopaminergic input from the ventrolateral periaqueductal gray (vlPAG)/dorsal raphe (DR). To date, no studies have examined the effects of chronic alcohol on this circuit.

Probing different paradigms of morphine withdrawal on sleep behavior in male and female C57BL/6J mice.

Unlabelled: Opioid misuse has dramatically increased over the last few decades resulting in many people suffering from opioid use disorder (OUD). The prevalence of opioid overdose has been driven by the development of new synthetic opioids, increased availability of prescription opioids, and more recently, the COVID-19 pandemic. Coinciding with increases in exposure to opioids, the United States has also observed increases in multiple Narcan (naloxone) administrations as life-saving measures for respiratory depression, and, thus, consequently, naloxone-precipitated withdrawal.

The effects of electronic nicotine vapor on voluntary alcohol consumption in female and male C57BL/6 J mice.

Significance: Alcohol drinking and nicotine vaping often co-occur and dependence on both substances is common. However, the impact of nicotine vaping on alcohol consumption is not fully understood.

Methods: We examined the effects of nicotine vaping on ethanol drinking in female and male C57BL/6 J mice using an electronic nicotine delivery system and intermittent access two-bottle choice (IA-2BC) drinking.

Toll-like receptor 3 neuroimmune signaling and behavior change: A strain comparison between Lewis and Wistar rats.

There are many unanswered questions about the interaction between the immune system and behavior change, including the contributions of individual differences. The present study modeled individual differences in the immune system by comparing inbred Lewis rats, which have dysregulated stress and immune systems, to their genetically diverse parent strain, Wistar rats. The objective was to examine the consequences of an immune challenge on behavior and neuroimmune signaling in both strains.

Effect of progesterone administration in male and female smokers on nicotine withdrawal and neural response to smoking cues: role of progesterone conversion to allopregnanolone.

Background: Progesterone administration has therapeutic effects in tobacco use disorder (TUD), with females benefiting more than males. Conversion of progesterone to the neurosteroid allopregnanolone is hypothesized to partly underlie the therapeutic effects of progesterone; however, this has not been investigated clinically.

Methods: Smokers (n = 18 males, n = 21 females) participated in a randomized, double-blind, placebo-controlled crossover study of 200 mg progesterone daily across 4 days of abstinence.

Short-term transcriptomic changes in the mouse neural tube induced by an acute alcohol exposure.

Alcohol exposure during the formation and closure of the neural tube, or neurulation (embryonic day [E] 8-10 in mice; ∼4th week of human pregnancy), perturbs development of midline brain structures and significantly disrupts gene expression in the rostroventral neural tube (RVNT). Previously, alcohol exposure during neurulation was found to alter gene pathways related to cell proliferation, p53 signaling, ribosome biogenesis, immune signaling, organogenesis, and cell migration 6 or 24 h after administration. Our current study expands upon this work by investigating short-term gene expression changes in the RVNT following a single binge-like alcohol exposure during neurulation.

Predator odor (TMT) exposure potentiates interoceptive sensitivity to alcohol and increases GABAergic gene expression in the anterior insular cortex and nucleus accumbens in male rats.

Post-traumatic stress disorder (PTSD) confers enhanced vulnerability to developing comorbid alcohol use disorder (AUD). Exposure to the scent of a predator, such as the fox odor TMT, has been used to model a traumatic stressor with relevance to PTSD symptomatology. Alcohol produces distinct interoceptive (subjective) effects that may influence vulnerability to problem drinking and AUD.

Tauopathy and alcohol consumption interact to alter locus coeruleus excitatory transmission and excitability in male and female mice.

Alcohol use disorder is a major public health concern in the United States. Recent work has suggested a link between chronic alcohol consumption and the development of tauopathy disorders, such as Alzheimer's disease and frontotemporal dementia. However, relatively little work has investigated changes in neural circuitry involved in both tauopathy disorders and alcohol use disorder.

Cholinergic REST-G9a gene repression through HMGB1-TLR4 neuroimmune signaling regulates basal forebrain cholinergic neuron phenotype.

Lipopolysaccharide (LPS) and high-mobility group box 1 (HMGB1) are Toll-like receptor (TLR4) agonists that activate proinflammatory neuroimmune signaling linked to loss of basal forebrain cholinergic neurons (BFCNs) and cognitive deficits. Loss of choline acetyltransferase immunoreactive (ChAT + IR) BFCNs is generally interpreted as cell death, but recent studies find anti-inflammatory interventions restore adolescent ethanol exposure-induced persistent loss of adult ChAT + IR neurons and cognitive deficits, suggesting proinflammatory signaling-induced reversible gene repression of ChAT in BFCNs. Using an Wistar rat basal forebrain slice culture (FSC) model to investigate TLR4 involvement in repression of the BFCN phenotype, we report that direct TLR4 activation with LPS decreases expression of multiple BFCN markers in the absence of observable neuronal loss or cell death.