Further, Adcy1tg mice show reduced immobility under acute physical stress conditions in the forced swimming test and are more sensitive to the antidepressant desipramine. Our results demonstrate a novel function of Adcy1 in stress coping and suggest Adcy1 as a potential target to antagonize stress vulnerability and promote antidepressant efficacy.Following oxycodone (Oxy) conditioned place preference (CPP), delta opioid receptors (DORs) differentially redistribute in hippocampal CA3 pyramidal cells in female and male rats in a manner that would promote plasticity and opioid-associative learning processes. However, following chronic immobilization stress (CIS), males do not acquire Oxy-CPP and the trafficking of DORs in CA3 pyramidal neurons is attenuated. Here, we examined the subcellular distribution of DORs in CA1 pyramidal cells using electron microscopy in these same cohorts.

Saline (Sal)-females compared to Sal-males have more cytoplasmic and total DORs in dendrites and more DOR-labeled spines. Following Oxy-CPP, DORs redistribute from near-plasmalemma pools in dendrites to spines in males.

Control females compared to control males have more near-plasmalemmal dendritic DORs. Following CIS, dendritic DORs are elevated in the cytoplasm in females and near-plasmalemma in males.

CIS Sal-females compared to CIS Sal-males have more DORs on the plasensitivity to DOR agonists. Conversely, CIS plus behavioral enrichment does not alter DORs in CA1 pyramidal cells in males, which may contribute to their diminished capacity to acquire Oxy-CPP.Since its development in 1993, the Trier Social Stress Test (TSST) has been used widely as a psychosocial stress paradigm to activate the sympathetic nervous system and hypothalamic-pituitary-adrenal axis (HPAA) stress systems, stimulating physiological functions (e.g. heart rate) and cortisol secretion. Several methodological variations introduced over the years have led the scientific community to question replication between studies. In this systematic review, we used the Preferred Reporting Items of Systematic Reviews and Meta-Analysis (PRISMA) to synthesize procedure-related data available about the TSST protocol to highlight commonalities and differences across studies. We noted significant discrepancies across studies in how researchers applied the TSST protocol. In particular, we highlight variations in testing procedures (e.g., number of judges, initial number in the arithmetic task, time of the collected saliva samples for cortisol) and discuss possible misinterpretation in comparing findings from studies failing to control for variables or using a modified version from the original protocol. Further, we recommend that researchers use a standardized background questionnaire when using the TSST to identify factors that may influence physiological measurements in tandem with a summary of this review as a protocol guide. More systematic implementation and detailed reporting of TSST methodology will promote study replication, optimize comparison of findings, and foster an informed understanding of factors affecting responses to social stressors in healthy people and those with pathological conditions.Several lines of evidence suggest that antidepressant drugs may act by modulating neuroplasticity pathways in key brain areas like the hippocampus. We have reported that chronic treatment with fasudil, a Rho-associated protein kinase inhibitor, prevents both chronic stress-induced depressive-like behavior and morphological changes in CA1 area. Here, we examined the ability of fasudil to (i) prevent stress-altered behaviors, (ii) influence the levels/phosphorylation of glutamatergic receptors and (iii) modulate signaling pathways relevant to antidepressant actions. 89 adult male Sprague-Dawley rats received intraperitoneal fasudil injections (10 mg/kg/day) or saline vehicle for 18 days. Some of these animals were daily restraint-stressed from day 5-18 (2.5 h/day). 24 hr after treatments, rats were either evaluated for behavioral tests (active avoidance, anxiety-like behavior and object location) or euthanized for western blot analyses of hippocampal whole extract and synaptoneurosome-enriched fractions. We report that fasudil prevents stress-induced impairments in active avoidance, anxiety-like behavior and novel location preference, with no effect in unstressed rats. Chronic stress reduced phosphorylations of ERK-2 and CREB, and decreased levels of GluA1 and GluN2A in whole hippocampus, without any effect of fasudil. However, fasudil decreased synaptic GluA1 Ser831 phosphorylation in stressed animals. Additionally, fasudil prevented stress-decreased phosphorylation of GSK-3β at Ser9, in parallel with an activation of the mTORC1/4E-BP1 axis, both in hippocampal synaptoneurosomes, suggesting the activation of the AKT pathway. Our study provides evidence that chronic fasudil treatment prevents chronic stress-altered behaviors, which correlated with molecular modifications of antidepressant-relevant signaling pathways in hippocampal synaptoneurosomes.The ability of an individual to reduce the intensity, duration or frequency of a stressor is a critical determinant of the consequences of that stressor on physiology and behavior. To expand our understanding of the brain networks engaged during controllable and uncontrollable stress and to identify sex differences, we used functional connectivity analyses of the immediate early gene product Fos in male and female rats exposed to either controllable or uncontrollable tail shocks. Twenty-eight regions of interest (ROI) were selected from the structures previously evinced to be responsible for stress response, action-outcome learning, or sexual dimorphism. We found that connectivity across these structures was strongest in female rats without control while weaker connectivity was evident in male rats with control over stress. Smad inhibitor Interestingly, this pattern correlates with known behavioral sex differences where stressor controllability leads to resilience in male but not female rats. Graph theoretical analysis identified several structures important to networks under specific conditions. In sum, the findings suggest that control over stress reshapes functional connectivity.