Oral physiology and oral processing behaviors each influence bolus formation and potentially eating rate. However, the role of oral physiology on intake among adults with a healthy dentition remains unclear. Here, we examined associations between physiological measures (salivary flow rate and masticatory performance), oral processing behaviors (bolus formation and eating rate), and pretzel intake. In a single laboratory session, adults (n=68, 66% women) completed assessments of salivary flow rate (parafilm), masticatory performance (gum mixing task), and bolus formation (mini-pretzels). Bolus formation was evaluated with and without metronome guided chewing, and expectorated boluses were assessed for cohesiveness. Eating rate (g/min) was quantified from video recordings during consumption of pretzels (70 g) and a fixed portion of 30 g carrots. Pretzel intake was measured as the difference between pre and post consumption weights of the pretzel portion. Self-reported eating rate was measured on a 101-point scale (0 to 100, anchored with Extremely Slow and Extremely Fast). Higher salivary flow rate associated with a more cohesive bolus, while masticatory performance showed a marginal association with carrot eating rate but not with pretzel eating rate, bolus cohesiveness, or pretzel intake. Self-reported eating rate was significantly associated with measured eating rate for both carrots and pretzels, but not with pretzel intake. For pretzels, larger bite sizes and faster eating rate were both associated with greater pretzel intake, with men exhibiting larger bite sizes, faster eating, and greater consumption than women. Collectively, these data confirm that eating rate and bite size influence pretzel intake, while also showing minimal evidence that the physiological measures used here directly influence eating rate or pretzel intake.
Fibromyalgia (FM) is a chronic syndrome characterized by widespread pain, frequently accompanied by cognitive deficits and psychiatric symptoms. FM has been associated with large-scale functional alterations of brain networks involved in pain processing, particularly the default mode network (DMN) and the pain salience network. The infralimbic cortex (IL), a region of the medial prefrontal cortex (mPFC) considered part of the DMN, is functionally connected to regions involved in salience processing. However, the role of the IL in modulating FM-related manifestations remains poorly understood. Therefore, the objective of this study was to investigate the effect of IL neurostimulation on pain modulation and anxiety- and depression-like behaviors in an experimental rat model of FM. IL neurostimulation was performed using a deep-brain stimulation (DBS) device (20 μA/100 Hz/15 s) 14 days after the experimental induction of FM using the reserpine pharmacological model (1 mg/kg, s.c., once daily for three consecutive days). IL neurostimulation reduced mechanical allodynia in the von Frey test and decreased both anxiety- and depression-like behaviors assessed using the open field, splash, and forced swim (FST) tests. These findings suggest that the IL exerts an inhibitory role in the modulation of pain and psychiatric comorbidities in FM, suggesting potential circuits between the IL and the salience network in modulating the manifestations of FM.
Individual differences in behaviour and cognition are increasingly recognized as a central component of animals' cognitive processes, yet their neurobiological basis remains poorly understood in fish. Here, we investigated behavioural and cognitive individuality in juvenile European seabass (Dicentrarchus labrax) using an integrative approach combining behavioural assessment in an inhibitory control test (cylinder test) and analysis of gene expression in the telencephalon. Although successful inhibitory control responses were rare, consistent individual differences emerged in exploration, persistence and coping style throughout all experimental phases. Inter-individual variability remained stable and was organised along a continuous gradient of stress coping styles, ranging from more reactive to more proactive profiles, rather than fitting into discrete categories. At the neurobiological level, transcriptomic analyses revealed two opposing gene sets: one associated with neuronal activation and synaptic plasticity, and the other related to neuroendocrine regulation and the stress response, showing partial and non-linear correspondences with the observed behavioural profiles. Taken together, these findings support the view of individuality as an emergent and multidimensional trait in European seabass and suggest that performance in cognitive tasks should be interpreted by considering inter-individual variation in behaviour and the associated neurobiological correlates.
Diabetes is a chronic disease characterized by hyperglycemia. It is associated with a variety of co-morbidities, including depression. This link is likely mediated in part by hyperglycemia-induced increases in inflammation. Given that exercise can benefit diabetes, inflammation, and depression, the aim of this study was to investigate if exercise may treat hyperglycemia-induced neuroinflammation and depressive-like behavior. We used the STZ model of hyperglycemia in male C57BL/6J mice and voluntary wheel running as exercise. To circumvent possible STZ-induced issues with wheel running, we provided mice with wheels for 10 days prior to STZ. Unexpectedly, we observed that 10 days of wheel access was sufficient to blunt development of STZ-induced hyperglycemia as well as most STZ-induced behavioral and inflammatory effects. Mice continued to show mild hyperglycemia, impaired glucose tolerance, and intermediate levels of insulin. No significant behavioral differences were observed. Increases in liver Tnf mRNA expression, but not TNF protein, were noted without changes in Il6 or Il1b. There were no changes in hippocampal Tnf or Il1b. We observed an interesting interaction for Bdnf, such that exercise increased expression in VEH but not STZ mice. This may indicate a neural response to mild hyperglycemia, though additional studies are required to confirm this effect. Overall, these data suggest that 10 days of voluntary exercise is sufficient to blunt STZ-induced hyperglycemia. This model may be useful in investigating the chronic effects of pre-diabetic blood glucose levels on brain health.
Individuals with anorexia nervosa (AN) consistently show lower fat intake and preference than healthy controls. Whether this avoidance is accompanied by altered orogustatory detection of dietary fatty acids (FAs) across chemical classes is unknown. In this pilot study, we measured psychophysical detection thresholds for lauric (C12:0, saturated), oleic (C18:1, monounsaturated), and linoleic (C18:2, polyunsaturated) acids in 50 healthy controls (76% female) and seven women with restrictive AN (rAN) using a forced choice ascending procedure (0.001-100 mM). rAN participants were reassessed at days 66 and 99 of treatment. We replicated the bimodal distribution of linoleic acid thresholds in controls (Hartigan's D= 0.102, p < .001), with a 53% taster proportion consistent with prior work. Women with rAN detected all three FAs at substantially lower concentrations than female controls (all pFDR ≤ .019; rank-biserial r range -.534 to -.835), with no detectable FA-type-specific modulation. Treatment effects could not be reliably estimated due to attrition. Although the small clinical sample limits mechanistic inference, the absence of FA-type specificity is compatible with, but does not establish, generalised orogustatory sensitisation, which may represent a clinically relevant dimension of fat aversion in rAN.
Sex hormones play a central role in the expression of sexually selected traits and reproductive behaviors in reptiles, yet experimental evidence linking specific hormonal changes to male phenotype and subsequent female mate choice remains limited. Here, we manipulated male sex hormones to test the effects of testosterone and estradiol on male coloration, behavior and female association patterns in the white-striped grass lizard (Takydromus wolteri). Twenty-three males were assigned to testosterone, estradiol, and control (olive oil) treatments, and female responses were quantified using association time in mate-choice trials. We also measured reflectance of male body colouration before and after treatments at six morphological regions. Treatment with estradiol resulted in a marked reduction in male body colour brightness across multiple regions, whereas testosterone treatment did not alter coloration relative to controls. Female association patterns were weak overall; however, non-gravid females showed a marginal tendency to avoid estradiol-treated males, while gravid females exhibited no preferences or avoidance. Hormone treatments did not significantly affect male boldness, activity, or locomotor performance. Together, these results suggest that visual traits on male T. wolteri are particularly sensitive to estradiol, and that female mate assessment is conservative and dependent on their current reproductive state. Sexual selection in this species appears to act primarily through hormone-mediated visual cues rather than through short-term hormonal effects on male behaviour.
This review aims to clarify the mechanistic links between sleep deprivation, appetite regulation, and insulin sensitivity, and to explore the role of melatonin in these pathways. A systematic search identified 82 relevant studies, which were critically and thematically analysed. Evidence indicates that sleep deprivation lowers melatonin levels, which impairs insulin sensitivity via disruptions in the IRS/PI3K/AKT and cAMP/PKA/CREB pathways. Melatonin interventions appear to influence these pathways and affect leptin and appetite-regulating neuropeptides such as POMC, AgRP, and NPY, although findings on the direction of these effects remain mixed. Intervention studies using melatonin doses of ≤5 mg/day for at least four weeks show potential for reducing body weight in humans. Overall, this review highlights the complex interactions between sleep deprivation, appetite regulation, insulin sensitivity, and obesity, and suggests that melatonin may offer a promising adjunctive approach, although further research is needed to resolve conflicting results and support evidence based practice.
Exercise provides broad health benefits, including improved emotional well-being and cognitive function. Emerging evidence suggests that exercising at different times during the day can have differential effects. However, how circadian phase and sex influence behavioral and physiological responses to exercise remains unclear. To address this question, we examined male and female wild-type mice maintained in either regular (REG, lights on/off at 7AM/7PM) or inverted (INV, lights off/on at 10AM/10PM) light/dark cycles. Mice were subjected to daily 20-min group swimming exercise sessions for 3 weeks, with each swimming session starting 2-3 h after the morning light change. Exercised mice and sedentary controls were then subjected to an open field test (OFT) and blood corticosterone (CORT) measurements 24 hours post-exercise. We quantified several observed behaviors during swimming: escape attempts, floating, climbing and collisions. We also identified a highly stereotypical behavior: floating with only nostrils-above-water events (NAWEs). We found that expression of these behaviors was differentially modulated by sex, light-cycle phase and their interaction. Notably, behavioral differences were more pronounced in REG mice (rest phase). REG mice also lost weight after exercise and had elevated CORT levels compared to mice kept in INV conditions (active phase). Interestingly, OFT exploratory behaviors showed significant differences primarily in INV mice, particularly females. Our novel findings reveal that circadian rhythms and sex significantly interact to modulate behavioral responses to group swimming exercise in wild-type mice. This emphasizes the need to consider the animals' circadian phase when designing preclinical studies to match intended behavioral and physiological outcomes.
BACKGROUND:Autonomic pain responses show substantial inter-individual variability, yet the role of personality in their temporal dynamics remains poorly understood. This study examined, in an exploratory analysis, whether Big Five personality traits - and conscientiousness in particular - are associated with the trajectory of blood-pressure responses to repeated noxious thermal stimulation. METHODS:Sixty-two healthy adults (33 men, 29 women; mean age 28.1 years, SD 6.7, range 19-40) underwent repeated thermal pain across four stimulation segments and three pain-related phases. Epoch-level mean blood pressure (MBP), derived from continuous non-invasive blood-pressure recording, was used as the physiological outcome, and ΔMBP was computed relative to the non-noxious Low phase. Linear mixed-effects models screened all five personality domains for an interaction with stimulus repetition (Segment), including stimulation phase and adjusting for age, sex, and subjective pain (ΔCoVAS); estimated marginal means were evaluated at representative conscientiousness levels (±1 SD). RESULTS:Of the five domains, only conscientiousness showed a nominally significant Segment × trait interaction (standardized β = 0.39 per SD; raw-score β = 0.018, p = .024). The segment trajectory was non-monotonic, and the conscientiousness-related difference was concentrated at one transition (S2→S3), where a steep decline at lower conscientiousness was markedly attenuated at higher conscientiousness. The linear interaction was attenuated when a by-subject random Segment slope was added, whereas the categorical interaction remained significant, indicating a non-linear, segment-specific pattern rather than robust linear moderation. Conscientiousness did not predict subjective pain (ΔCoVAS). Age was negatively associated with ΔMBP (p = .044) and, in sensitivity analyses, also moderated the segment trajectory. CONCLUSIONS:In this exploratory study, conscientiousness was associated with the temporal dynamics of pain-evoked blood-pressure responses - specifically a non-linear, segment-specific feature of the trajectory that was not paralleled by subjective pain. The findings highlight a potential role for personality in the temporal regulation of pain-related autonomic responses and require replication.
Collective panic is an important factor influencing emergency responses in underground environments; however, most existing studies assume homogeneous individuals and lack objective physiological validation. This study proposes a personality-modulated panic dynamics framework based on immersive virtual reality evacuation experiments conducted in a subway environment, integrating multimodal physiological measurements. Participants performed virtual reality emergency response tasks under panic emotional arousal and non-arousal conditions, during which skin conductance level (SCL) and electroencephalography (EEG) signals were recorded. Relative power changes in the θ, α, and β frequency bands were extracted, and personality traits were quantified using the OCEAN model. A Panic Composite Index (PCI) was constructed using principal component analysis (PCA) to quantify individual panic intensity. Based on this index, a dynamic panic evolution model incorporating external hazard stimuli and personality-modulated feedback regulation mechanisms was established and calibrated using regression analysis. Results indicate that extraversion significantly influences autonomic arousal, while conscientiousness and neuroticism modulate EEG responses in the θ and β bands, reflecting differences in cognitive control and stress responses during panic emotional arousal. Simulation results demonstrate that, under continuous external stimulation, individual panic states exhibit a rapid-response and gradual-stabilization pattern. Meanwhile, individuals with different personality traits display distinct panic-state evolution trajectories. Sensitivity analysis further confirms the robustness and stability of the proposed model. The proposed framework integrates physiological evidence with dynamic modeling, providing a quantitative approach for characterizing heterogeneous emotional arousal responses and offering theoretical insights into risk perception and emergency safety management in underground spaces.
Depression is a multifactorial, chronic, and recurrent psychiatric disorder that represents a major global health burden. Despite extensive research, its underlying neurobiological mechanisms remain incompletely understood, largely due to ethical and methodological limitations in human studies. Consequently, rodent models have become indispensable tools for investigating the neurobiology of depression and evaluating potential antidepressant therapies. This narrative review provides a comprehensive and updated overview of the principal experimental models of depression in mice and rats, including stress-based (learned helplessness, chronic unpredictable mild stress, early-life stress, and social defeat), surgical (olfactory bulbectomy), pharmacological, and genetic models. For each model, commonly used induction procedures, behavioral validation methods, neurobiological relevance, and the concepts of face, construct, predictive, and translational validity are discussed together with their major strengths and limitations. Although a formal systematic literature search was not performed, the selection of studies was guided by a focused review of the most widely cited and methodologically robust literature in the field, with an emphasis on recent advances and persistent controversies. The review also summarizes the behavioral paradigms most frequently used to assess depression-like phenotypes, including the forced swim test, tail suspension test, sucrose preference test, open field test, and complementary behavioral assays. Particular attention is given to current discussions regarding the interpretation and translational relevance of several behavioral tests, and the ongoing debate regarding the translational validity of the forced swim and tail suspension tests is explicitly acknowledged. Additionally, methodological issues such as reproducibility and protocol variability are discussed, and the influence of sex differences on model outcomes and behavioral responses is considered, given their growing clinical and preclinical relevance. Although no single animal model fully reproduces the complexity and heterogeneity of human depression, each model contributes to understanding specific neurobiological mechanisms underlying the disorder. A major challenge that remains is the frequent failure to translate promising preclinical findings into effective clinical therapies. Future progress in depression research will likely depend on integrating complementary animal models with multidimensional behavioral assessments while carefully considering these translational limitations to improve the clinical relevance of preclinical findings.
Spontaneous physical activity (SPA) represents a behavioral component contributing to energy dissipation and metabolic balance. However, it remains untested whether a cage-dimension-induced increase in SPA can mitigate the deleterious effects of high-fat diet-induced obesity in mouse models. This study aimed to evaluate metabolic outcomes in C57BL/6 mice housed in small (SC) or large cages (LC) and fed either AIN-93 M (control diet; CD) or a lard-enriched high-fat diet (HFD). Differential housing and diets began at 40 days of age (adolescent phase) and were maintained for 8 weeks. While animals in the SC groups had a floor space of 49.5 cm² per animal, those in the LC groups were provided with 267.9 cm² per animal, approximately five times larger. As expected, HFD feeding induced multiple detrimental effects compared with CD-fed mice; however, many of these effects were partially attenuated by LC housing. This is supported by the following findings: LCHFD mice, despite consuming a high-fat diet, exhibited increased recorded dark-phase SPA, reduced visceral fat accumulation (epididymal and retroperitoneal), lower fasting glucose levels, and higher muscle glycogen stores compared with SCHFD mice. Lower triglyceride stores in LCHFD mice also suggest that HFD-induced ectopic fat deposition may be attenuated by LC, although this effect appears to be muscle-specific, being evident in the quadriceps femoris but not in other muscles. Our findings provide an interesting translational insight suggesting that creating environments that encourage SPA may help attenuate metabolic impairments caused by a high-fat diet.
As obesity rates continue to rise globally, combination therapies are being developed for their pronounced and sustained weight loss effects. CagriSema is a fixed-ratio combination of the long-acting GLP-1R agonist semaglutide and the calcitonin (CTR)/amylin receptor (AMYR) agonist cagrilintide that shows greater efficacy for weight loss compared to GLP-1R and CTR/AMYR mono-agonists alone. However, knowledge of the neural sites capable of producing potentiated effects as a result of GLP-1R/CTR/AMY co-agonism remains incomplete. In this study, we investigate the laterodorsal tegmental nucleus (LDTg) as a central site of integration for GLP-1R and CTR/AMYR signaling, and explore the effect of co-agonism in this nucleus on feeding behavior. We first performed fluorescence in situ hybridization (FISH) to show that glp-1r- and ctr-expressing neurons comprise largely distinct populations within the LDTg, supporting a model where LDTg GLP-1R and CTR/AMYR agonists reduce feeding via engagement of distinct complementary cells in the LDTg. We also showed that co-administration of GLP-1R and CTR/AMYR agonists into the LDTg resulted in a greater suppression of food intake and reduction in body weight compared to either treatment alone. Finally, using an operant model, we found that this combinatorial treatment significantly reduced motivation to self-administer a highly palatable food reward. Overall, intra-LDTg co-agonism of GLP-1Rs and CTR/AMYRs produced a greater suppressive effect on homeostatic and motivational aspects of feeding behavior than monotherapy alone. These results highlight the LDTg as a previously undescribed central site with potential clinical relevance for the development of dual GLP-1R and CTR/AMYR pharmacotherapies to combat obesity.
Opioid exposure during adolescence, a critical neurodevelopmental period, can impair adult cognitive function through lasting neurobehavioral changes. Here, the effects of sub-chronic adolescent exposure to morphine (SAEM) on anxiety, fear conditioning, and synaptic plasticity in the ventral hippocampal CA1 field in adulthood were investigated. Adolescent male Wistar rats received escalating doses of morphine (2.5-12.5 mg/kg) for 5 days. Thereafter, open field and elevated plus maze tests were conducted, along with body weight was monitored during the experiment, and behavior was followed from adolescence to adulthood. Fear conditioning was performed using the passive avoidance test, and synaptic plasticity was assessed using extracellular field potential recordings in vitro. We found that SAEM did not significantly affect weight gain during the treatment period; however, it was associated with reduced weight gain in the subsequent four weeks. SAEM, specifically impaired fear conditioning and synaptic plasticity, despite showing no significant effects on locomotor activity, or anxiety-like behavior, as assessed in adulthood. Baseline synaptic responses did not differ significantly between the SAEM and control groups. However, SAEM increased the mean excitatory postsynaptic field potential (fEPSP) slopes required to produce half‑maximal population spike amplitude and reduced LTP in the ventral CA1 during adulthood. In sum, sub-chronic exposure to morphine during adolescence can persistently affect synaptic plasticity and cognitive function in adults.
High-altitude exposure disrupts sleep, but the temporal dynamics remain poorly defined. This study characterises time‑dependent changes in sleep architecture, HPA axis function, inflammation, and central sleep‑regulatory molecules during subacute hypobaric hypoxia. Male Sprague‑Dawley rats were exposed to simulated 7000 m for 1, 3, 5, or 7 days (H1d–H7d). Sleep was recorded by wireless EEG/EMG. HPA axis hormones, inflammatory cytokines, and sleep‑regulatory molecules were measured in serum, hippocampus, and hypothalamus. Multi‑dimensional integration was performed using principal component analysis (PCA). Hypoxia progressively reduced total sleep time and sleep efficiency, increased REM sleep percentage, and fragmented wakefulness, accompanied by declines in SWS delta power and REM theta power. The HPA axis exhibited peripheral–central dissociation: serum ACTH increased, whereas hippocampal ACTH and CORT were suppressed. Peripheral inflammation followed a time‑dependent pattern: an early IL‑6 surge (H1d), sustained Th1 suppression (IL‑12), and delayed IL‑10 elevation (H7d). Hippocampal BDNF, GABA, and histamine progressively declined; hypothalamic PGD₂, orexin A, 5‑HT, and histamine similarly decreased, while dopamine increased at H5d–H7d. PCA indicated a temporal separation between H3d and H5d, suggesting a transition from compensation to decompensation (mean Q² = 0.43). Subacute hypobaric hypoxia is associated with a time‑dependent transition from compensation to decompensation, characterised by sleep architecture collapse, HPA axis uncoupling, phased inflammation, and progressive loss of central sleep‑regulatory molecules. These findings offer a descriptive framework for understanding high‑altitude sleep disorders.
Across one's lifetime, heavy alcohol use during adolescence confers the highest risk for developing an alcohol use disorder (AUD), and therefore understanding its impact on the adolescent brain is essential for advancing effective interventions. Preclinical models are critical for investigations into the long-term neurobiological consequences of adolescent alcohol exposure with current mouse paradigms capturing either modest alcohol levels through voluntary consumption or high alcohol levels through passive exposure methods. The current study investigates the outcome of a mixed model of adolescent alcohol exposure by combining volitional adolescent alcohol intake using 2-bottle choice interleaved with alcohol vapor exposure. Our results show that 2 cycles of alcohol vapor elevate alcohol consumption and compulsive-like drinking behavior when measured in late adolescence, without affecting adult alcohol consumption. Neural activation patterns measured through c-Fos expression following adult alcohol consumption demonstrated that adolescent alcohol vapor exposed mice had increased activity in NAc core and CeA, with sex-dependent effects seen in PFC activation. We conclude that mixed alcohol consumption and vapor paradigms have short-term behavioral consequences and long-term neural effects.
The endovanilloid N-arachidonoyl dopamine (N-ADA) is a lipid mediator associated with nociception and inflammation, but its effects on reward and anxiety remain unclear. We examined the behavioral impact of subacute N-ADA pre-exposure on conditioned place preference (CPP) and anxiety-like behavior in the circular open-field test (COF), assessed both under basal conditions and after acute CB1 blockade/GPR55 modulation with rimonabant. Male BALB/c mice were pre-exposed for four days to either vehicle (10% ethanol) or N-ADA (0.1 mg/kg). A counterbalanced CPP protocol was then conducted over eight days. Place preference was assessed before and after rimonabant administration (0.1 mg/kg), and anxiety-like behavior was evaluated using the COF following rimonabant. N-ADA exposure alone did not significantly modify place preference compared to baseline (p > 0.05). However, following rimonabant administration, N-ADA-exposed mice displayed a significant increase in preference for the drug-paired compartment (p < 0.05) and increased anxiety-like behavior in the COF (p < 0.05). These findings indicate that prior exposure to N-ADA can influence reward- and anxiety-related behaviors specifically under conditions of CB1 blockade/GPR55 modulation. The results support the modulatory role of N-ADA on reward- and anxiety-related behaviors at the dose tested, indicating an interaction with endocannabinoid signaling (or other rimonabant-sensitive mechanisms).
Acute sleep loss is associated with elevated fatigue, decreased energy, and impaired cognitive functioning. Acute exercise has shown promise in reducing detriments to daytime functioning following sleep loss. The primary purpose of this study was to examine the effects of a single bout of moderate-intensity aerobic exercise on neurocognitive function following acute sleep restriction. A secondary aim was to examine the effects of exercise in psychological aspects of daytime functioning, including arousal, fatigue, energy, and sleepiness following acute sleep restriction. Age-and sex-matched participants (N = 56; Mage = 21.8 ± 2.5 years) were randomly assigned to an exercise or control (i.e., seated rest) condition. Following an acute 4-hour sleep restriction protocol, participants completed an oddball paradigm with concurrent electroencephalographic (EEG) recording before and after exercise or seated rest. P3 amplitude and latency, response accuracy and reaction time (RT), arousal, sleepiness, energy, and fatigue were assessed. No significant P3 or behavioral performance differences were observed by condition. The exercise group reported increased daytime functioning, as reflected by increased energy (Cohen's d = 0.69) and arousal (Cohen's d = 0.94) and decreased fatigue (Cohen's d = -0.79) and sleepiness (Cohen's d = -0.95) compared to the control group. Findings indicate that a single bout of moderate-intensity aerobic exercise following acute sleep restriction enhances psychological aspects of daytime functioning, while no changes in neurocognitive function were observed. The null neurocognitive result should be interpreted with caution, as it may reflect the limited cognitive demand of the oddball task or insufficient statistical power to detect small effects rather than a true absence of exercise-related benefit.
Alcohol Use Disorder (AUD) is a leading risk factor for negative health consequences associated with disruptions in neural functions. While ethanol-induced neuronal adaptations have remained in the spotlight for researchers investigating AUD, growing evidence highlights glial cell populations and their contributions to AUD pathology. This review explores the role of oligodendrocytes (OLs) and their progenitors (OPCs) in ethanol-induced alterations of white matter (WM), myelin structure, composition, and integrity. Human neuroimaging studies reveal reductions in WM volume and microstructural integrity, accompanied by molecular evidence of impaired myelin architecture and lipid composition in postmortem brains. Preclinical models provide causal evidence linking ethanol to dose-, length of exposure-, and brain-region-dependent dysregulation of OLs at transcriptional, structural, and metabolic levels. Investigations of the underlying mechanisms implicate oxidative stress, neuroinflammation, transcriptional changes, epigenetic modifications, and lipid dysregulation as key pathways through which ethanol disrupts OLs. Because OLs are essential for proper myelination, neural function, and brain connectivity, ethanol-induced changes in these processes likely contribute to the cognitive, learning, and emotional deficits associated with AUD. Investigations into prenatal and adolescent ethanol exposure reveal impairments in OL maturation and myelination that produce long-lasting deficits which persist into adulthood. Together, these findings support ethanol-induced OL dysregulation and circuit disruption as drivers in AUD pathology. Understanding how ethanol impacts OLs and OPCs at both molecular and developmental levels is critical for identifying novel therapeutic targets aimed at ameliorating disruptions to WM integrity, diagnosing AUD, and improving outcomes for individuals impacted by AUD.
Recent research indicates that odor cues may contribute to the detection or discrimination of sugar solutions, highlighting an important variable for gustatory researchers to consider. However, whether animals can directly detect volatile compounds emitted by sugar solutions has not yet been systematically tested. Further, studies in both rodents and humans have, thus far, utilized limited concentrations of these tastants, preventing gustatory researchers from fully assessing the potential impact of odor on their specific experiment. To address these shortcomings, we have performed a rigorous psychophysical examination of the orthonasal olfactory sensitivity of mice to the volatiles emanating from reagent-grade sugar solutions using a head-fixed Go / No-Go operant conditioning assay combined with highly reproducible stimulus delivery. C57BL/6J (WT) mice displayed high sensitivity to glucose (0.05M) and fructose (0.07M) but were slightly less sensitive to sucrose (0.14M). This phenomenon was not dependent upon canonical sweet taste signaling, as mice lacking the T1R3 subunit (T1R3KO) of the "sweet" taste receptor did not differ in their olfactory sensitivity to glucose as compared to WT mice. As these carbohydrates have negligible volatility, mice are likely responding to volatile contaminants associated with the tastants. These estimates of olfactory sensitivity to sugar solutions should be considered in the design and interpretation of taste-based paradigms in mice. Moreover, gustatory function, in general, should be evaluated in light of potential contributions from the olfactory system.
