The nucleus reuniens: a key node in the neurocircuitry of stress and depression.

The hippocampus and prefrontal cortex (PFC) are connected in a reciprocal manner: whereas the hippocampus projects directly to the PFC, a polysynaptic pathway that passes through the nucleus reuniens (RE) of the thalamus relays inputs from the PFC to the hippocampus. The present study demonstrates that lesioning and/or inactivation of the RE reduces coherence in the PFC-hippocampal pathway, provokes an antidepressant-like behavioral response in the forced swim test and prevents, but does not ameliorate, anhedonia in the chronic mild stress (CMS) model of depression. Additionally, RE lesioning before CMS abrogates the well-known neuromorphological and endocrine correlates of CMS. In summary, this work highlights the importance of the reciprocal connectivity between the hippocampus and PFC in the establishment of stress-induced brain pathology and suggests a role for the RE in promoting resilience to depressive illness.

Effects of different electron donor feeding patterns on TCE reductive dechlorination performance.

This study investigates how the feeding pattern of e(-) donors might affect the efficiency of enhanced in situ bioremediation in TCE-contaminated aquifers. A series of lab-scale batch experiments were conducted using butyrate or hydrogen gas (H2) as e(-) donor and a TCE-dechlorinating microbial consortium dominated by Dehalococcoides spp. The results of these experiments demonstrate that butyrate is similarly efficient for TCE dechlorination whether it is injected once or in doses. Moreover, the present work indicates that the addition of butyrate in great excess cannot be avoided, since it most likely provide, even indirectly, significant part of the H2 required. Furthermore, methanogenesis appears to be the major ultimate e(-) accepting process in all experiments, regardless the e(-) donor used and the feeding pattern. Finally, the timing of injection of H2 seems to significantly affect dechlorination performance, since the injection during the early stages improves VC-to-ETH dechlorination and reduce methanogenic activity.

Modelling microbial dechlorination of trichloroethene: investigating the trade-off between quality of fit and parameter reliability.

This work puts forth a heuristic approach for investigating compromises between quality of fit and parameter reliability for the Monod-type kinetics employed to model microbial reductive dechlorination of trichloroethene. The methodology is demonstrated with three models of increasing fidelity and complexity. Model parameters were estimated with a stochastic global optimization algorithm, using scarce and inherently noisy experimental data from a mixed anaerobic microbial culture, which dechlorinated trichloroethene to ethene completely. Parameter reliability of each model was assessed using a Monte Carlo technique. Finally, an alternate quantity of applied interest was evaluated in order to assist with model discrimination. Results from the application of our approach suggest that the modeler should examine the implementation of conceptually simple models, even if they are a crude abstraction of reality, as they can be computationally less demanding and adequately accurate when model performance is assessed with criteria of applied interest, such as chloroethene elimination time.

The presence of Merkel cell polyomavirus is associated with deregulated expression of BRAF and Bcl-2 genes in non-small cell lung cancer.

Polyomaviruses such as BK virus (BKV), JC virus (JCV) and Merkel cell polyomavirus (MCPyV) are typically nononcogenic, although they have been detected in a variety of human neoplasms. The aim of our study was to determine the frequency of the most common polyomaviruses MCPyV, BKV and JCV as well as the gene expression profile of genes involved in oncogenesis including K-ras, BRAF, RKIP, Bax, Bcl-2, p53 and RB1 in a cohort of non-small cell lung cancer (NSCLC) patients. Real-time and nested polymerase chain reaction (PCR) were used to assess the presence of polyomaviruses DNA in tissue biopsies from 110 patients with primary NSCLC and 14 tissue specimens from macroscopically healthy sites of their lung. Real-time PCR was also used to determine the mRNA expression of K-ras, BRAF, RKIP, Bax, Bcl-2, p53 and RB1 in selected samples. Results showed that ten NSCLC specimens were positive for the presence of MCPyV DNA (10/110, 9.1%), whereas no control sample was tested positive for the virus. The MCPyV-positive samples were predominantly obtained from male smokers (9/10). BKV and JCV DNA were not detected either in lung tissues biopsies or the control specimens. Interestingly, gene expression analysis revealed increased mRNA and protein expression of BRAF gene in association with BRAF phosphorylation in the MCPyV-positive samples, whereas Bcl-2 gene expression was downregulated in the same type of samples. The detected MCPyV prevalence in NSCLC in combination with the deregulated expression of BRAF and Bcl-2 genes suggests that these events are likely to contribute to the pathogenesis of NSCLC.

Polymorphisms and haplotypes in MyD88 are associated with the development of sarcoidosis: a candidate-gene association study.

Sarcoidosis is considered as a disorder of protracted immune response to an as yet unidentified causative agent that leads to granuloma formation. Material from M. tuberculosis and P. acne has been repeatedly detected in the sarcoidosis lesions, implying the involvement of the Toll-like receptor2 (TLR2) gene that responds to these intracellular pathogens. Since TLR2 association studies have produced controversial results, we sought to investigate whether the downstream signalling molecule MyD88 could be linked to disease susceptibility. We analyzed a total of 93 cases with sarcoidosis and of 89 controls for the most common MyD88 SNPs: -938C>A (rs4988453) and 1944C>G (rs4988457). There is evidence that the genotype distributions of both variants are associated with the development of sarcoidosis (p = 0.038 for -938C>A and p = 0.026 for 1944C>G). In particular, -938A and 1944G carriers were associated with risk of sarcoidosis [OR = 2.48 (1.23-5.02) and OR = 0.33 (0.14-0.76)], respectively, indicating dominance of the mutant alleles; however, the adjustment of the effect size for age and sex diminished the significance. The haplotype analysis showed association for the -938A/1944G haplotype (p < 0.001). Since genetic association studies have linked MyD88 to Hodgkin's lymphoma it is tempting to speculate that MyD88 may contribute to the granuloma formation that characterizes sarcoidosis.

Effect of wastewater chlorination on endocrine disruptor removal.

Endocrine disrupting chemicals (EDCs) are compounds of mainly anthropogenic origin that interfere with the endocrine system of animals and humans thus causing a series of disorders. Wastewater treatment plants are one of the major routes for transporting such chemicals to the water courses. In the context of this study, several chlorination batch tests were performed in order to assess the effectiveness of chlorination to remove bisphenol A (BPA), triclosan (TCS), nonylphenol (NP) and its ethoxylates (NP1EO and NP2EO) from secondary effluent. According to the results, an appreciable removal of NP, BPA and TCS to the order of 60-84% was observed as an effect of moderate chlorination doses. This was not the case for NP1EO and NP2EO as even at high chlorine doses, removal efficiencies were lower (37% for NP1EO and 52% for NP2EO). Removal efficiencies of NP, BPA and TCS are practically independent of contact time, although this was not the case for NP1EO and NP2EO. Based on toxicity experiments, it is anticipated that following chlorination of the target chemicals, production of more toxic metabolites is taking place. Therefore the effectiveness of chlorination to remove EDCs is questionable and more research is needed to guarantee safe wastewater reuse.

Assessing feasibility of targeted primary care referrals for patients with clinical suspicion of interstitial lung disease using lung ultrasound: a prospective case finding study. The potential benefits of LUS utilization.

BACKGROUND: In Primary Health Care (PHC) many interstitial lung disease (ILD) cases may remain at diagnostic delay, due to their challenging presentation and the limited experience of general practitioners (GPs) in recognizing their early symptoms. OBJECTIVE: We have designed a feasibility study to investigate early ILD case-finding competency between PHC and tertiary care. METHODS: A cross-sectional prospective case-finding study was launched at two private health care centers of Heraklion, Crete, Greece, during nine months (2021-2022). After clinical assessment by GP, PHC attenders, who agreed to participate in the study, were referred to the Respiratory Medicine Department, University Hospital of Heraklion, Crete, underwent Lung Ultrasound (LUS) and those with an overall suspicion for ILDs underwent high resolution computed tomography (HRCT) scan. Descriptive statistics and chi-square tests were used. Multiple Poisson regression analysis was performed to explain positive LUS and HRCT decision with selected variables. RESULTS: One hundred and nine patients out of 183 were finally included (54.1% females; mean age 61, SD: 8.3 years). Thirty-five (32.1%) were current smokers. Overall, two out of ten cases were assessed to need HRCT due to a moderate or high suspicion (19.3%; 95%CI 12.7, 27.4). However, in those who had dyspnea in relation to counterparts, a significantly higher percentage of patients with LUS findings (57.9% vs. 34.0%, p=0.013) was found, as in those who had crackles (100.0% vs. 44.2%, p= 0.005). Detected possible ILD provisional labelling cases were 6, and most importantly, 5 of those cases were considered highly suspicious for further evaluation based on LUS findings. CONCLUSIONS: This is a feasibility study exploring potentials by combining data of medical history, basic auscultation skills, as crackles detection, and inexpensive and radiation-free imaging technique, such as LUS. Cases of ILD labeling may be hidden within PHC, sometimes, much before any clinical manifestation.

Prevalence of pulmonary hypertension in patients with idiopathic pulmonary fibrosis: correlation with physiological parameters.

The aim of this study was to prospectively evaluate the prevalence of pulmonary hypertension (PH) in patients with idiopathic pulmonary fibrosis (IPF). One hundred thirty-nine patients (101 male, mean age = 68.6 ± 9 years), with confirmed IPF and who were admitted to eight Pulmonary Departments in Greece between November 2005 and December 2006 were included in the study. Pulmonary artery systolic pressure (PASP) was estimated by echocardiography, and PH was defined as PASP > 36 mmHg. We compared demographics, pulmonary function tests, NYHA functional status, 6-min walk distance (6MWD), B-type natriuretic peptide (BNP), PaO(2), and P(A-a)O(2) at rest data between patients with PH and without PH (PASP ≤ 36 mmHg). Increased estimated right ventricular systolic pressure was present in 55% of patients (mean PASP = 47.1 ± 11.2 mmHg vs. 30.3 ± 3.8 mmHg, respectively). Patients with PH had a lower but not statistically significant DL(CO) (47.1 ± 18.8 vs. 52.5 ± 20.1), lower PaO(2) at rest (64.6 ± 12.2 vs. 71.1 ± 11.3, P = 0.004), and lower mean 6MWD (282 ± 118 vs. 338 ± 91, P = 0.007). Significant differences were also observed in the NYHA functional status between the two groups (P = 0.02). Statistically significant correlations were observed between PASP and PaO(2) at rest (r = -0.331, P = 0.00), P(A-a)O(2) at rest (r = 0.494, P = 0.00)(,) 6MWD (r = -0.264, P = 0.01), SpO(2) at rest (r = -0.293, P = 0.00), SpO(2) at the end of exercise (r = -0.364, P = 0.00), and also BNP values (r = 0.319, P = 0.01). Moreover, PaO(2) (P = 0.02), P(A-a)O(2) (P = 0.005), and SpO(2) at the end of exercise (P = 0.023) were independent predictors of the presence of estimated PH. Using Doppler echocardiography as a screening tool for the estimation of PH, we found that PH is common in patients with IPF. Gas exchange parameters at rest and exercise desaturation might indicate underlying PH in IPF.

Pivotal clinical dilemmas in collagen vascular diseases associated with interstitial lung involvement.

The connective tissue disorders (CTDs), also called collagen vascular diseases (CVDs), represent a heterogeneous group of immunologically mediated inflammatory disorders with a large variety of affected organs. Individuals with a CTD (rheumatoid arthritis, systemic lupus erythematosus, systemic sclerosis, Sjögren's syndrome, polymyositis/dermatomyositis and mixed connective tissue disease) are susceptible to respiratory involvement. When the lungs are affected, an increasing mortality and morbidity in CVDs occurs. Interstitial lung disease (ILD) is established as a clinical corollary across the spectrum of CTDs, with an overall incidence estimated at 15%. Therefore, pivotal clinical dilemmas remain in the evaluation and management of ILD involvement in CVDs. Critical questions are the presence of fibrosis and whether the disease is clinically significant. Moreover, the clinician has to decide if treatment is warranted and which is the best therapeutic approach. The use of additional tests, such as pulmonary function tests, high-resolution computed tomography scan, bronchoalveolar lavage fluid and surgical lung biopsy, deserves better discussion. The present review focuses on establishing the diagnosis of ILD in CTD, and on evaluating disease activity and prognosis. This will provide the basis for therapeutic decisions that will be discussed, including an overview of recent advances.

Duloxetine-induced hypomania: case report and brief review of the literature on SNRIs-induced mood switching.

Manic switching during antidepressant treatment has been reported with every class of antidepressant drugs. Serotonin-noradrenaline reuptake inhibitors (SNRIs) have been increasingly used for the treatment of unipolar and bipolar depression and are well tolerated and sufficiently effective because of their dual mechanism of action. A case of duloxetine-induced hypomania in a non-bipolar patient is presented, and a brief review of all cases of SNRIs' induced mania and hypomania has been carried out. The available data suggest that SNRIs, especially venlafaxine, can induce mood switching in patients with bipolar depression and in certain patients with unipolar depression, but the potential of duloxetine and milnacipran to induce manic or hypomanic symptoms cannot be disregarded. Switching appears to be dose-related and treatment initiation with lower doses and upward titration when needed may be preferable in selected cases and may help minimizing the risk of mood switching.

Scleroderma lung disease: evolving understanding in light of newer studies.

PURPOSE OF REVIEW: To review therapeutic goals in pulmonary fibrosis in systemic sclerosis in the light of pathogenetic thinking and therapeutic data, with particular attention to recent data questioning the importance of the identification of alveolitis. RECENT FINDINGS: Immunological/inflammatory activation remains the primary therapeutic target, based on recent data. Other effective therapies have not been developed, despite investigation of many pathogenetic pathways. In most cases, lung disease is predominantly fibrotic and prevention of progression is the only practicable therapeutic goal. Indications for introducing treatment remain uncertain. A granulocytosis on bronchoalveolar lavage and ground-glass attenuation on computed tomography, previously thought to denote an inflammatory histological picture ('alveolitis'), are usually indicative of fibrotic disease. By contrast, a recent staging system, integrating computed tomography and pulmonary function data, might, with refinement, identify patients likely to benefit from treatment. SUMMARY: Treatment benefits consist of the prevention of progression and are largely confined to patients with extensive pulmonary fibrosis. Historical algorithms for the identification of alveolitis, using computed tomography and bronchoalveolar lavage, are inaccurate and do not identify patients most likely to benefit from treatment. Accurate prognostic evaluation by staging the severity of lung disease remains central to management and will be a major focus of future studies.

Individual responses to novelty are associated with differences in behavioral and neurochemical profiles.

Experimental animals can be differentiated on the basis of their horizontal or vertical activity to high responders (HR) and low responders (LR) upon exposure to a novel environment. These individual differences have been associated with behavioral and neurobiological differences in a number of experimental procedures used for studying sensitivity to psychostimulants, anxiety, depression, and cognitive function. In the present study, we differentiated the rats to HR and LR based on their vertical activity upon exposure to a novel environment. Additionally, we ascertained whether HR and LR rats differ in a battery of tests such as passive avoidance (PA), object recognition (OR), and the water-maze (WM) that provide indices for cognitive function and the forced swim test (FST), an animal model of affective responsivity and antidepressant-like activity. Potential differences in neurochemical indices between the two phenotypes were also examined. HR rats displayed impaired non-spatial object recognition memory, but enhanced spatial performance, as compared to LR rats. FST induced "depressive-like" symptoms in both phenotypes that were differently manifested in HR versus LR rats. Neurochemical findings revealed distinct differences in serotonergic and dopaminergic activity in the striatum and the prefrontal cortex of HR as compared to LR rats. The above results show that HR and LR rats exhibit important differences in a battery of tests related to cognitive performance or affective responsivity, which may be associated with differences in certain neurobiological parameters.

Sex differences in the effects of two stress paradigms on dopaminergic neurotransmission.

Sex differences in behavioral and neurobiological responses to stress are considered to modulate the prevalence of some psychiatric disorders, including major depression. In the present study, we compared dopaminergic neurotransmission and behavior in response to two different stress paradigms, the Forced Swim Test (FST) and the Chronic Mild Stress (CMS). Male and female rats were subjected to one session of swim stress for two consecutive days (FST) or to a variety of mild stressors alternating for six weeks (CMS). Subsequently, the tissue levels of dopamine (DA) and its metabolites (HVA and DOPAC) in the hippocampus, the hypothalamus, the prefrontal cortex and the striatum were measured using high-performance liquid chromatography (HPLC). The ratios HVA/DA and DOPAC/DA were also calculated as indices of the dopaminergic activity. Results from the FST determined that males exhibited lower immobility, higher climbing duration and increased dopaminergic activity in the prefrontal cortex and the hippocampus compared to females. CMS induced alterations in sucrose intake in both sexes, while it only decreased dopaminergic activity in the prefrontal cortex of females. These findings show that FST and CMS have different effects on the dopaminergic activity of discrete brain regions depending on the sex of the animal. These data support the growing evidence that females display a differential response and adaptation to stress than males.

Microsatellite DNA analysis does not distinguish malignant from benign pleural effusions.

Distinguishing malignant from benign pleural effusions using routine cytology is a common diagnostic problem. Recently, genetic alterations, including microsatellite instability (MSI) and loss of heterozygosity (LOH), have been described in malignant pleural effusions and proposed as methods improving diagnostics. The purpose of this study was to evaluate a panel of molecular markers for the detection of genetic alterations of cells in pleural effusions and to determine their diagnostic value as an additional test to cytologic examination. Pleural fluid and peripheral blood from 48 patients (36 male and 12 female, median age 71 years) were analyzed. Twenty-six patients had malignant pleural effusion, including 23 lung cancer and three metastatic non-pulmonary carcinoma. The control group consisted of 22 patients with benign pleural effusions. Only 14 malignancy-associated pleural effusions were cytology-positive for malignant cells (54%), whereas all benign pleural effusions were negative. DNA was extracted from all the samples and analysed for MSI and/or LOH using the following microsatellite markers: D3S1234, D9S171, D12S363, D17S250, D5S346 and TP53Alu, located at five chromosomal regions: 3p, 9p, 12q, 17q, 5q. Microsatellite analysis of the pleural fluid pellet exhibited genetic alterations in two neoplastic pleural fluid cases and in one inflammatory case. Two out of 26 (7.6%) patients with malignant pleural effusion showed genetic alterations. One exhibited MSI in three different microsatellite markers (D17S250, D9S171, D3S134) and the other showed LOH in marker D3S134. One out of 22 (4.5%) patients with benign pleural effusion showed LOH in marker D3S134. In conclusion, genetic alterations at the level of microsatellite DNA, were detected only in very few cases of malignant pleural effusions, and in one case of benign pleural effusion. Thus, our data suggest that microsatellite DNA analysis does not facilitate the diagnosis of malignant pleural effusion.

Infliximab therapy in pulmonary fibrosis associated with collagen vascular disease.

OBJECTIVE: To study the potential effectiveness of tumor necrosis factor a (TNF-alpha) inhibitor treatment for pulmonary fibrosis associated with a collagen vascular disease, CVD (rheumatoid arthritis, RA and systemic sclerosis, SSc) refractory to conventional treatment. METHODS: Four patients (three men with RA, one woman with SSc) were treated with infliximab. All patients received 3mg/kgr of infliximab at intervals 0, 2 and 6 weeks, and then maintenance infusions every 8 weeks afterwards for at least a 12-month period. Patients had active disease despite treatment with corticosteroids and other immunomodulatory agents. RESULTS: Treatment was well-tolerated from all patients. Pulmonary fibrosis remained stable during treatment in terms of symptoms, pulmonary function tests (PFTs) and High resolution computed tomography (HRCT) appearance. As expected, a clinical response was observed in joint symptoms in patients with RA as evaluated by the DAS28 (Disease Activity Score, the 28 joint version). CONCLUSION: This study suggests that inhibition of TNF-alpha with infliximab may stabilize the progression of pulmonary fibrosis associated with CVD. Prospective, controlled trials are necessary to determine the efficacy of infliximab in pulmonary fibrosis associated CVD.

Impaired mRNA Expression of the Migration Related Chemokine Receptor CXCR4 in Mesenchymal Stem Cells of COPD Patients.

Defective tissue repair and remodeling are main aspects of Chronic Obstructive Pulmonary Disease (COPD) pathophysiology. Bone marrow mesenchymal stem cells (BM-MSCs) have been implicated in this direction, as their functional impairment and recruitment could possibly contribute to disease development and progression. The present study characterizes for the first time the expression of migration related chemokine receptors and their ligands in BM-MSCs from COPD patients. CXCR4/SDF1a and CCR7/CCL19-CCL21 mRNA levels were evaluated in BM-MSCs obtained from twelve COPD patients and seven healthy donors. SDF1a protein levels in sera and BM-MSCs' conditioned media were also evaluated. CXCR4, SDF1a, CCL19, and CCL21 mRNA levels were significantly reduced in COPD BM-MSCs while CCR7 levels were undetectable. Notably, SDF1a protein levels were marginally elevated in both patient sera and BM-MSCs' conditioned media while the increase in SDF1a serum levels significantly correlated with disease severity in COPD. Our findings show posttranscriptional regulation of SDF1a levels in BM-MSCs of COPD patients and significant downregulation of SDF1a and CXCR4 mRNA indicating an involvement of the SDF1a signaling pathway in the disease pathophysiology.

Clearance of technetium-99m-DTPA in pulmonary sarcoidosis.

BACKGROUND: The aim of this study was to explore the possible association of the lung clearance of 99mTc-DTPA scan with HRCT lung abnormalities and with the pulmonary function tests [PFTs] in patients with sarcoidosis. METHODS: We studied prospectively 15 patients [5 males, 10 females] of median age 46yr [range 27-67] with histologically proved sarcoidosis. HRCT scoring included the sum of the severity and extent of lymph node enlargement and parenchymal involvement. RESULTS: The mean DTPA clearance half-time [tau 1/ <40 min] was found [mean [SD]] 38.3+/-4.5min. The lymph node enlargement was found 34% and the parenchymal involvement 12%. DTPA clearance was negatively correlated with the parenchymal involvement [r= -0.651, p=0.0091]. The HRCT parenchymal abnormalities were found significantly correlated with PFTs [FVC [r= -0.65, p=0.008] and TLCO [r= -0.76, p=0.02]. CONCLUSIONS: Our data suggest a moderate association between 99mTc-DTPA scan and HRCT in pulmonary sarcoidosis. However, further studies in large scale of sarcoid patients are needed to clarify the role of this novel methodology in the evaluation and follow-up of this disorder.

Combined Pulmonary Fibrosis and Emphysema in Scleroderma-Related Lung Disease Has a Major Confounding Effect on Lung Physiology and Screening for Pulmonary Hypertension.

OBJECTIVE: To assess the prevalence of combined pulmonary fibrosis and emphysema (CPFE) in systemic sclerosis (SSc) patients with interstitial lung disease (ILD) and the effect of CPFE on the pulmonary function tests used to evaluate the severity of SSc-related ILD and the likelihood of pulmonary hypertension (PH). METHODS: High-resolution computed tomography (HRCT) scans were obtained in 333 patients with SSc-related ILD and were evaluated for the presence of emphysema and the extent of ILD. The effects of emphysema on the associations between pulmonary function variables and the extent of SSc-related ILD as visualized on HRCT and echocardiographic evidence of PH were quantified. RESULTS: Emphysema was present in 41 (12.3%) of the 333 patients with SSc-related ILD, in 26 (19.7%) of 132 smokers, and in 15 (7.5%) of 201 lifelong nonsmokers. When the extent of fibrosis was taken into account, emphysema was associated with significant additional differences from the expected values for diffusing capacity for carbon monoxide (DLco) (average reduction of 24.1%; P < 0.0005), and the forced vital capacity (FVC)/DLco ratio (average increase of 34.8%; P < 0.0005) but not FVC. These effects were identical in smokers and nonsmokers. Multivariate analysis showed that the presence of emphysema had a greater effect than echocardiographically determined PH on the FVC/DLco ratio, regardless of whether it was analyzed as a continuous variable or using a threshold value of 1.6 or 2.0. CONCLUSION: Among patients with SSc-related ILD, emphysema is sporadically present in nonsmokers and is associated with a low pack-year history in smokers. The confounding effect of CPFE on measures of gas exchange has major implications for the construction of screening algorithms for PH in patients with SSc-related ILD.

Chronic mild stress impact: are females more vulnerable?

Despite the knowledge that women are more susceptible than men to stress-related mental illness, such as major depression, there is no comprehensive estimation of the role of gender in the detrimental effects of chronic stress that might cause depression. Sex differences regarding the association of behavioral parameters with serotonergic and hypothalamic-pituitary-adrenal axis activities were investigated in the chronic mild stress model of depression. Additionally, the impact of chronic mild stress exposure on an additional/novel short-term stressful procedure, such as the forced swim test was examined in male and female rats. Female rats were found to be more vulnerable to chronic mild stress and that was depicted with disruption of sucrose intake, decreases in open field activity, increased corticosterone levels, alteration in estrous cycle and decreased serotonergic activity in hippocampus and hypothalamus. On the contrary, in males the current chronic mild stress protocol elicited only behavioral changes, such as disruption in sucrose intake and decreased open field activity. Interestingly, in response to forced swim test, females previously subjected to chronic mild stress, were found to cope better by exhibiting increased active behavior in the second forced swim test session and higher hypothalamic serotonergic activity in comparison with corresponding males. On the other hand, males were more affected by previous chronic mild stress exposure and that was manifested by decreased active behavior in the first forced swim test session and increased corticosterone levels following second forced swim test session. These data indicate that although females are more vulnerable in the application of chronic mild stress than males, in response to an additional-novel stressor (forced swim test) they show better response. Therefore, both sex/gender and combination of stressful procedures should be carefully considered in the study of the pathophysiology of stress-related mental illnesses.

Somatostatin receptors in the ventral pallidum/substantia innominata modulate rat locomotor activity.

RATIONALE: Somatostatin and its receptors (sst(1) and sst(2)) have been localized in brain nuclei implicated in motor control, such as the nucleus accumbens, ventral pallidum (VP) and substantia innominata (SI). OBJECTIVES: The objective of the study is to investigate the effect of somatostatin and selective sst(1) and sst(2) analogs infused in the VP/SI on the locomotor activity of the rat. METHODS: Somatostatin (15, 30, 60, 120 and 240 ng/0.5 microl/side), CH275 (sst(1) analog; 60, 180, 240 and 480 ng/0.5 microl/side), MK678 (sst(2) analog; 120, 240 and 480 ng/0.5 microl/side), L-809,087 (sst(4) agonist, 240 ng/0.5 microl/side) or saline (vehicle) were infused bilaterally in the VP/SI of the rat and locomotor activity measured for 60 min. The effect of SRA-880 (sst(1) antagonist) and CYN-154806 (sst(2) antagonist) on somatostatin-, CH275- and MK678-mediated locomotor activity was also ascertained. RESULTS: Somatostatin decreased locomotor activity in the first 30 min after its infusion in the VP/SI and in a dose-dependent manner. The sst(1) and sst(2) antagonists, SRA-880 and CYN-154806, respectively, reversed the somatostatin effect. The sst(1) and sst(2) agonists CH275 and MK678, respectively, mimicked somatostatin's actions, while the selective sst(4) agonist L-809,087 had no effect. Moreover, SRA-880 and CYN-154806 reversed the respective agonist action on locomotor activity. CONCLUSION: The present study provides functional evidence for the presence of sst(1) and sst(2) receptors in the VP/SI and their implication in motor control. The mechanism via which somatostatin and agonists mediate the attenuation of locomotor activity is presently being investigated.