Frontiers in Behavioral Neuroscience最新文献

Maladaptive avoidance is a central feature of many mental disorders, particularly stress- and anxiety-related disorders. Those disorders are more prevalent in women, suggesting that there may be sex differences in avoidance propensity. Sex differences have been documented in threat conditioning, but not in active avoidance paradigms, despite their potential clinical relevance. Preclinical research has historically focused on males, limiting our understanding of the neurobiological mechanisms underlying sex differences in threat responses. To address this gap, we investigated sex-specific strategies in adult Long Evans rats (10 female, 9 male) using a platform-mediated avoidance (PMA) task that created a high-conflict choice between reward-seeking and safety. Behavior was tracked over 25 days, with analyses focusing on a stable performance phase (days 20-25) objectively defined using change point analysis. Females consistently prioritized safety, spending significantly more time foregoing reward to avoid foot shock and retreating earlier to the safe zone. Males engaged in more persistent reward-seeking despite the risk of shock. This difference was not driven by differential reward motivation. Furthermore, female strategies were not significantly modulated by the estrous cycle. These results were consistent in a pre-registered replication study. Thus, male and female rats employ fundamentally different strategies to resolve approach-avoidance conflict: females adopt a robust, safety-first strategy, while males demonstrate a risk-prone, reward-oriented approach. Identifying the neural mechanisms underlying these differences may guide more targeted interventions for anxiety and trauma-related disorders.

Introduction: Cocaine use disorder (CUD) is highly comorbid with alcohol and nicotine use, yet preclinical research rarely models polysubstance use or incorporates clinically relevant variables such as social and biological factors. This study utilized an animal model of relapse, cocaine-induced reinstatement, under a drug vs. food choice procedure; the effect of co-use of nicotine was also examined. Cocaethylene, the active metabolite formed when alcohol and cocaine are co-used, was also examined with and without nicotine co-use.

Methods: Socially housed male (N = 12) and female (N = 10) cynomolgus monkeys, all with experience self-administering cocaine or cocaethylene under a concurrent drug vs. food schedule of reinforcement, were studied after drug choice was extinguished by studying saline vs. food choice (< 20% drug choice).

Results: In Experiment 1, both cocaine (0.01-0.3 mg/kg, i.v.) and cocaethylene (0.03-0.3 mg/kg, i.v.) pretreatments reliably increased drug-associated choice; dominant monkeys of both sexes showed greater reinstatement following cocaine and cocaethylene pretreatments when compared to subordinates. Cocaine was also more potent than cocaethylene regardless of sex or social rank. In Experiment 2, nicotine (0.01-0.056 mg/kg) was co-administered with saline, cocaine or cocaethylene. Nicotine alone increased drug-associated choice only in females and selectively increased cocaine-induced drug-associated choice only in females, regardless of social rank. Nicotine did not significantly alter cocaethylene-induced reinstatement, although a trending increase was observed in females.

Discussion: Thus, social rank impacts cocaine- and cocaethylene-induced reinstatement, and the effects of nicotine were influenced by sex. This underscores the value of translational models that move beyond single-drug approaches and suggest that especially in women with CUD, abstaining from nicotine would increase the likelihood of remaining abstinent from cocaine.

Most animals and humans are inherently social, enabling group dynamics to promote survival. Despite their importance, how the brain calibrates appropriate social behaviors to maximize survival and benefits remains incompletely understood. Distributed networks of neural circuits mediate complex behavioral states, including social behaviors. The striatum has long-known to be a structure essential for motivation and goal-directed behavior. The striatum is massive: it extends far along the anterior-posterior axis and can be divided into ventral, dorsal, and posterior domains. While it is well-appreciated that these striatal domains control motivated behaviors through coordinated functions, such that ventral striatum (e.g., nucleus accumbens) governs motivation and rewards processing, dorsal striatum mediates motor planning and action selection, and the posterior striatum (i.e., tail of the striatum) integrates sensory inputs, much less is understood about how they modulate social interactions. This mini review discusses the current understanding of what aspects of social behavior are controlled by each striatal subregion. We focus on key studies that highlight prominent neuromodulators, such as dopamine, serotonin, and neuropeptides, and their roles in social behaviors. We propose a framework in which striatal subregions calibrate social interaction through coordinated activities that mediate distinct aspects of the social interaction, similar to general motivation. A deeper understanding of how distributed striatal circuits modulate social behavior will help inform the development of therapeutic approaches for social dysfunction in various psychiatric states.

Adolescence is a critical developmental stage marked by profound physical, emotional, and social transformations. During this stage, bodily changes, emotional vulnerability, environmental stimuli, and cultural influences may expose adolescents to behaviors that appear unpredictable or maladaptive. Moreover, a central aspect of adolescence is the drive for self-affirmation, which often manifests through aggression, in actions, thoughts, and interpersonal relationships. More than merely an individual reaction, adolescent aggression also constitutes a broader social phenomenon. The present work seeks to explore the contemporary role played by aggression in adolescence and its varied expressions. It supports a paradigm in which adolescent aggression fluctuates between two poles: one aligned with the pleasure principle, characterized by self-gratifying behavior that disregards others and seeks unmediated satisfaction; and the other aligned with the reality principle, characterized by self-affirming behavior grounded in moral consciousness and respect for social norms. The dominance of either form of aggression plays a crucial role in shaping adolescent development. In contemporary society, cultural models and myths promote a narcissistically driven, empathy-deficient form of aggression. This mode of behavior, which is socially rewarded and normalized, risks becoming the adolescent's internalized version of the reality principle, with success achieved at the expense of others. Such a framework may inhibit the transformation of aggression into socially and morally attuned behavior. Thus, it is essential to understanding adolescent aggression as a powerful, though ambivalent, force in the human development.

Introduction: Research has implicated mesocorticolimbic glutamate transmission in alcohol use. The current study focused on glutamate transmission within two key sub-regions, i.e., prelimbic (PL) cortex and nucleus accumbens (NAc) shell, in mediating ethanol reinforcement and drinking in rats.

Methods: Intracranial self-administration (ICSA) was conducted to examine effects of inhibition of local glutamate transmission on ethanol ICSA into these sub-regions. Protein levels were determined with Western blot in both sub-regions of alcohol-preferring P and Wistar rats on key glutamate-related proteins that can regulate extracellular glutamate levels. Quantitative microdialysis was performed to measure basal extracellular glutamate concentrations and clearance in the PL cortex following chronic ethanol drinking. An additional study tested effects of centrally administered LDN-212320, a glutamate transporter 1 (GLT-1) activator, on ethanol drinking.

Results: Co-infusion of the metabotropic glutamate receptor 2/3 (mGluR2/3) agonist LY379268 with ethanol inhibited ethanol ICSA into these sub-regions. Expression of mGluR3, but not GLT-1, was lower in P than Wistar rats in both sub-regions. Ethanol drinking enhanced basal extracellular glutamate concentrations and reduced glutamate clearance. Intra-ventricular microinjection of LDN-212320 decreased ethanol drinking.

Discussion: These results suggest that (a) activation of local glutamate transmission is critical to ethanol reinforcement within the PL cortex and NAc shell, (b) strain difference exists in mGluR3 protein expression between P and Wistar rats, (c) chronic ethanol induces neuro-adaptations characterized by enhanced basal extracellular glutamate transmission, and (d) up-regulation of GLT-1 attenuates ethanol drinking. Taken together, these results further support the importance of glutamate transmission within the PL cortex and NAc shell in mediating ethanol effects.

Perioperative neurocognitive disorder (PND) is a prevalent and serious complication affecting the central nervous system following surgery, particularly among elderly patients. PND has a significant impact on patient prognosis and places a substantial burden on both individuals and the healthcare system. Despite its importance, the complex pathological mechanisms underlying PND remain inadequately understood, and there are currently no effective prevention or treatment strategies available. One critical factor contributing to PND is the imbalance in protein homeostasis, with the ubiquitin-proteasome system (UPS), recognized as the primary mechanism for protein quality control within cells. This review systematically discusses the crucial role of UPS dysfunction in the development of PND. Additionally, it analyzes potential biomarkers for diagnosing PND and explores treatment strategies targeting the UPS. This provides a new perspective for a deeper understanding of the molecular mechanisms involved in PND and lays a theoretical foundation for the development of new intervention methods.

Introduction: The rapid growth of short video platforms has raised concerns about their impact on users' mental health, particularly sleep quality. The aim of this research is to investigate the relationship between short video addiction and sleep quality among college students, examine the differential impacts of algorithm types (personalized vs. community-based) and content types on sleep parameters, and evaluate the effectiveness of a multi-component intervention.

Methods: Sixty college students (aged 18-25) meeting criteria for short video addiction (PSQI ≥5, daily usage ≥2 h) were randomly assigned to personalized algorithm (n = 30) or community-based algorithm (n = 30) groups. Sleep quality was measured using the Pittsburgh Sleep Quality Index (PSQI), actigraphy, and the Short Video Addiction Scale (SVA-S). The intervention combined cognitive behavioral therapy (CBT), digital technology tools (time-window control, brightness adjustment), and a social support system ("Sleep Guardian").

Results: Personalized algorithms significantly worsened sleep quality compared to community-based algorithms (PSQI: 10.4 ± 2.3 vs. 8.7 ± 2.1, p = 0.003, Cohen's d = 0.77). Entertainment content had the most detrimental effects on sleep parameters compared to knowledge and information content (p < 0.001, η² = 0.23). The multi-component intervention significantly improved sleep quality in both groups, with PSQI scores decreasing by 3.6 points in the personalized algorithm group and 2.8 points in the community-based group (p < 0.001, Cohen's d = 1.71 and 1.46, respectively). Daily short video usage decreased by 47.1% and 54.3%, respectively.

Conclusion: Short video addiction significantly impacts sleep quality. The combination of personalized algorithms and entertainment content creates particularly detrimental conditions for sleep. A comprehensive intervention incorporating CBT, digital tools, and social support effectively improves sleep quality and reduces addiction symptoms.