Social stress has emerged as one of the most impactful environmental risk factors contributing to psychiatric disorders in modern societies. Although acute stress responses are adaptive mechanisms that promote survival and homeostasis, chronic social stress induces maladaptive neurobiological changes that culminate in pathological behavioral phenotypes. Accumulating evidence from rodent studies demonstrates that chronic social stress reshapes neural circuits and disrupts neuroendocrine regulation. In this review, we summarize and compare major rodent models including early life stress, social isolation, chronic social defeat stress, and chronic subordinate colony housing, and synthesize how these paradigms differentially engage the hypothalamic–pituitary–adrenal axis and monoaminergic systems, including serotonergic, noradrenergic, and dopaminergic circuits, as well as emerging modulators such as endocannabinoids and neuropeptide Y. Because these paradigms engage distinct developmental windows and have been validated predominantly in males, we explicitly evaluate outcomes as a function of age at exposure and sex. We further integrate these neurochemical alterations into a synaptic and cell-type-specific framework of cortico-limbic circuit remodeling linking excitation/inhibition imbalance and astrocytic dysregulation to the divergence between susceptible and resilient phenotypes. We introduce allostatic load as an integrated framework linking cumulative, paradigm-specific stress burdens to vulnerability and resilience, and highlight active, compensatory neuroendocrine and circuit-level mechanisms that confer resilience. We propose that chronic social stress represents not a simple neurotransmitter deficit, but a dysregulation of neural circuits and neuroendocrine plasticity, providing a systems-level perspective of stress-related mental illness.
Maternal exposure to constant light during pregnancy (CLE) is associated with disrupted circadian organization and persistent behavioral alterations in adult offspring. This study examined behavioural performance and 24-hour locomotor activity patterns, as well as hippocampal pCREB and BDNF levels, in adult male and female offspring following prenatal CLE and maternal treatment with piromelatine (pir), which acts as an agonist at melatonin MT1/MT2 and serotonin 5-HT1A/5-HT1D receptors. Pregnant Wistar rats under light-dark regime received vehicle (veh), whereas dams exposed to CLE received vehicle (LL-veh), pir (10 mg/kg), or melatonin. Compared to the LL-veh groups, offspring from pir-treated dams exhibited reduced anxiety- and depression-like responses and improved working memory in both sexes. Individual-subject cosinor analysis revealed heterogeneous 24-hour locomotor rhythmicity within and between groups. No significant treatment-group effect was detected for MESOR or amplitude, and the descriptive acrophase patterns did not provide evidence of treatment-induced restoration or normalization of circadian organization. Maternal pir treatment was associated with higher hippocampal pCREB and BDNF levels in male, but not female offspring relative to the LL-veh group. While the behavioral and molecular differences occurred concurrently in males, these findings do not prove that pCREB/BDNF signaling mediated the behavioral outcomes. Furthermore, the study cannot distinguish the direct developmental effects of maternal pir exposure from those mediated through maternal or offspring circadian rhythm. Therefore, the findings should be interpreted as long-term behavioral and sex-specific molecular differences associated with maternal pir treatment rather than as evidence of circadian-independent antidepressant, anxiolytic, cognitive-enhancing, or BDNF-enhancing actions.
Real-world walking frequently requires pedestrians to maintain proactive inhibition to safely navigate unpredictable environments. While cortical modulations occurring during locomotion under environmental uncertainty are well-established, the specific proactive mechanisms underlying this state of inhibitory anticipation remain unexplored. This study aimed to investigate the behavioral and cortical shifts associated with anticipating a stop during overground walking. Fourteen healthy young adults performed fluent and cautious walking tasks with an expected stop. Cortical activity and trunk acceleration were recorded using a 32-channel mobile electroencephalography and an integrated accelerometer. Step-1 latency and step-interval variability were calculated via heel strike detection. Gait-phase-related power modulations were computed, and spectral principal component analysis was applied to attenuate artifacts. The results revealed that cautious walking significantly increased step-interval variability, whereas step-1 latency remained unaffected. At the cortical level, left frontotemporal areas exhibited an attenuated and delayed theta desynchronization during the swing phase. Furthermore, centroparietal regions demonstrated an altered temporal profile of alpha and beta synchronization, characterized by enhanced late-stance synchronization and reduced swing-phase synchronization. The present findings suggest that anticipating a potential stop may alter the rhythmic consistency of gait and reorganize phase-specific cortical dynamics. Being prepared to stop may shift the neural control of automated locomotion toward active monitoring, highlighting the relevance of proactive inhibition during everyday mobility.
Neural substrates playing a role in the development of sensitized behavioral responses after repeated methamphetamine exposure are not fully understood. In this study, we investigated the role of kappa opioid receptors (KORs) in the development of methamphetamine-induced locomotor sensitization, which is used as a rodent model for methamphetamine-induced sensitized behavioral responses. The study was conducted over 28 days using adult male and female rats. Methamphetamine (0.5 mg/kg; i.p.)-induced increase in locomotor activity was measured on Days 2 and 28. On Days 3–8, animals were treated with methamphetamine (1 mg/kg; i.p.) injections followed by a period of no drug administration (Days 9–27). Manipulation of KORs was done using the KOR agonist (U50488; 1.5 & 6 mg/kg; s.c.; Days 3–8) or the KOR antagonist (norBNI; 5 & 15 mg/kg; s.c.; Day 2; 2 h post meth injections) prior to methamphetamine (1 mg/kg) treatment on Days 3–8. Difference in total distance travelled on Day 28 from Day 2 after methamphetamine administration was used as measure of methamphetamine-induced locomotor sensitization. Pretreatment with norBNI (15 mg/kg but not 5 mg/kg) prior to repeated methamphetamine (1 mg/kg) treatment (Days 3–8) facilitated development of methamphetamine-induced locomotor sensitization in adult male, but not female rats. In contrast, pretreatment with U50488 (6 or 1.5 mg/kg) prior to repeated methamphetamine (1 mg/kg) treatment (Days 3–8) did not influence development of methamphetamine-induced locomotor sensitization in either adult male or female rats. Together, the data suggests differential sex-dependent effects of KOR blockade on the development of methamphetamine-induced locomotor sensitization.
