SALIVARY CORTISOL AND IMMUNOGLOBULIN A RESPONSES TO SIMULATED AND OFFICIAL JIU-JITSU MATCHES

Moreira, A, Franchini, E, Freitas, CG, Arruda, AFS, Moura, NR, Costa, EC, and Aoki, MS. Salivary cortisol and immunoglobulin A responses to simulated and official Jiu-Jitsu matches. J Strength Cond Res 26(8): 2185-2191, 2012-The aim of this study was to compare the salivary cortisol (sC) and the salivary immunoglobulin A (sIgA) responses to simulated and official Brazilian Jiu-Jitsu (BJJ) matches. Saliva samples were collected from 9 male BJJ athletes before (pre) and after (post) 2 simulated matches (SMs) and 2 official matches (OMs) performed during 2 different competitions. Salivary cortisol and sIgA concentrations (absolute concentration of sIgA [sIgA(abs)] and the secretion rate of sIgA [sIgA(rate)]) were measured by an enzyme-linked immunosorbent assay. For sC, there was an effect of condition (SM vs. OM) (p < 0.05) and a time effect (pre and post) (p < 0.05). The sC was lower during SMs as compared with that during OMs and lower at premeasurement when compared with postmeasurement. No changes were observed for sIgA measurements. In summary, both SMs and official BJJ matches can increase sC levels. Moreover, the higher sC resting levels, observed before OMs, suggest that psychological factors associated with high physical-physiological demands from official BJJ competitions maximize stress hormone responses. In addition, the present findings suggest that the acute effect of BJJ matches on mucosal immunity is minimal, and it seems unlikely that changes in cortisol play a major role in the alterations in sIgA levels in response to BJJ matches. The findings of this study suggest that the use of sC can provide valuable information for coaches regarding athletes' responses to competition. In addition, psychological strategies should be implemented before events, to improve the manner in which BJJ athletes cope with the stress inherent to official matches.

Quality and quantity of milk produced by Saanen goats submitted to stress during three sequential days

The experiment aimed to study the effect of physiological stress on cortisol levels, quality and quantity of milk through punctual administration of ACTH. Twelve Saanen goats were divided in two experimental groups: ACTH group (0,5 mu g of ACTH/Kg.L.W); Placebo group (placebo solution). Milk production, and percentages of protein, fat, lactose and SCC (somatic cells counting) of the milk were analyzed before, during and after the administration of ACTH/placebo. Simultaneously to the ACTH/placebo administration and during three sequential days, blood was collected to evaluate cortisol concentrations. At times -30 and zero, both groups presented basal concentrations of cortisol. The increase of cortisol contents was significant at times 60 (group ACTH: 59.00 +/- 5.70 and groups placebo: 5.23 +/- 1.37ng/mL) and 120 (group ACTH: 47.96 +/- 9.72 and group placebo: 4.38 +/- 1,14ng/mL) since the cortisol content was higher on the ACTH group. The values returned to the basal level at 300 minutes. Concerning milk production, no differences were found between ACTH and placebo groups. Milk, protein, fat, lactose and SCC did not distinguish one group from another. The results indicated that the physiological stress induced during three days was not harmful to milk production and milk quality of Saanen goats.

beta-ADRENOCEPTORS IN THE MEDIAL AMYGDALOID NUCLEUS MODULATE THE TACHYCARDIAC RESPONSE TO RESTRAINT STRESS IN RATS

In the present study, we investigated the involvement of beta-adrenoceptors in the medial amygdaloid nucleus (MeA) in cardiovascular responses evoked in rats submitted to an acute restraint stress. We first pretreated Wistar rats with the nonselective beta-adrenoceptor antagonist propranolol microinjected bilaterally into the MeA (10, 15, and 20 nmol/100 nL) 10 min before exposure to acute restraint. The pretreatment with propranolol did not affect the blood pressure (BP) increase evoked by restraint. However, it increased the tachycardiac response caused by acute restraint when animals were pretreated with a dose of 15 nmol, without a significant effect on the BP response. This result indicates that beta-adrenoceptors in the MeA have an inhibitory influence on restraint-evoked heart rate (HR) changes. Pretreatment with the selective beta(2)-adrenoceptor antagonist ICI 118,551 (10, 15, and 20 nmol/100 nL) significantly increased the restraint-evoked tachycardiac response after doses of 15 and 20 nmol, an effect that was similar to that observed after the pretreatment with propranolol at a dose of 15 nmol, without a significant effect on the BP response. Pretreatment of the MeA with the selective beta(1)-adrenoceptor antagonist CGP 20712 (10, 15, and 20 nmol/100 nL) caused an opposite effect on the HR response, and a significant decrease in the restraint-evoked tachycardia was observed only after the dose of 20 nmol, without a significant effect on the BP response. Because propranolol is an equipotent antagonist of both beta(1) and beta(2)-adrenoceptors, and opposite effects were observed after the treatment with the higher doses of the selective antagonists ICI 118,551 and CGP 20712, the narrow window in the dose-response to propranolol could be explained by a functional antagonism resulting from the simultaneous inhibition of beta(1) and beta(2)-adrenoceptors by the treatment with propranolol. The present results suggest that beta(2)-adrenoceptors have an inhibitory influence on the restraint-evoked tachycardiac response, whereas beta(1)-adrenoceptors have a facilitatory influence on the restraint-evoked tachycardiac response. (c) 2012 IBRO. Published by Elsevier Ltd. All rights reserved.

Chronic contamination assessment integrating biomarkers' responses in transplanted mussels-A seasonal monitoring

This study aimed to provide the first biomonitoring integrating biomarkers and bioaccumulation data in Sao Paulo coast, Brazil and, for this purpose, a battery of biomarkers of defense mechanisms was analyzed and linked to contaminants' body burden in a weigh-of-evidence approach. The brown mussel Perna perna was selected to be transplanted from a farming area (Caraguatatuba) to four possibly polluted sites: Engenho D'Agua, DTCS (Dutos e Terminais do Centro-Oeste de Sao Paulo) oil terminal (Sao Sebastiao zone), Palmas Island, and Itaipu (It; Santos Bay zone). After 3 months of exposure in each season, mussels were recollected and the cytochrome P4501A (CYP1A)- and CYP3A-like activities, glutathione-S-transferase and antioxidants enzymes (catalase, glutathione peroxidase, and glutathione reductase) were analyzed in gills. The concentrations of polycyclic aromatic hydrocarbons, linear alkylbenzenes, and nonessential metals (Cr, Cd, Pb, and Hg) in whole tissue were also analyzed and data were linked to biomarkers' responses by multivariate analysis (principal component analysisfactor analysis). A representation of estimated factor scores was performed to confirm the factor descriptions and to characterize the studied stations. Biomarkers exhibited most significant alterations all year long in mussels transplanted to It, located at Santos Bay zone, where bioaccumulation of organic and inorganic compounds was detected. This integrated approach using transplanted mussels showed satisfactory results, pointing out differences between sites, seasons, and critical areas, which could be related to land-based contaminants' sources. The influence of natural factors and other contaminants (e.g., pharmaceuticals) on biomarkers' responses are also discussed.

PARAVENTRICULAR AND SUPRAOPTIC NUCLEI OF THE HYPOTHALAMUS MEDIATE CARDIOVASCULAR RESPONSES EVOKED BY THE MICROINJECTION OF NORADRENALINE INTO THE MEDIAL AMYGDALOID NUCLEUS OF THE RAT BRAIN

The medial amygdaloid nucleus (MeA) is a part of the limbic system and is involved in cardiovascular modulation. We previously reported that microinjection of noradrenaline (NA) into the MeA of unanesthetized rats caused pressor and bradycardiac responses, which were mediated by acute vasopressin release into the systemic circulation. In the present study, we tested the possible involvement of magnocellular neurons of the paraventricular (PVN) and/or supraoptic (SON) of the hypothalamus that synthesize vasopressin in the cardiovascular pathway activated by the microinjection of NA into the MeA. Pressor and bradycardiac responses to the microinjection of NA (27 nmol/100 nL) into the MeA were blocked by pretreatment of either the PVN or the SON with cobalt chloride (CoCl2, 1 mM/100 nL), thus indicating that both hypothalamic nuclei mediate the cardiovascular responses evoked by microinjection of NA Into the MeA. Our results suggest that the pressor and bradycardiac response caused by the microinjection of NA into the MeA is mediated by magnocellular neurons in both the PVN and SON. (C) 2012 IBRO. Published by Elsevier Ltd. All rights reserved.

Rho-kinase inhibition attenuates airway responsiveness, inflammation, matrix remodeling, and oxidative stress activation induced by chronic inflammation

Possa SS, Charafeddine HT, Righetti RF, da Silva PA, Almeida-Reis R, Saraiva-Romanholo BM, Perini A, Prado CM, Leick-Maldonado EA, Martins MA, Tiberio ID. Rho-kinase inhibition attenuates airway responsiveness, inflammation, matrix remodeling, and oxidative stress activation induced by chronic inflammation. Am J Physiol Lung Cell Mol Physiol 303: L939-L952, 2012. First published September 21, 2012; doi:10.1152/ajplung.00034.2012.-Several studies have demonstrated the importance of Rho-kinase in the modulation of smooth muscle contraction, airway hyperresponsiveness, and inflammation. However, the effects of repeated treatment with a specific inhibitor of this pathway have not been previously investigated. We evaluated the effects of repeated treatment with Y-27632, a highly selective Rho-kinase inhibitor, on airway hyperresponsiveness, oxidative stress activation, extracellular matrix remodeling, eosinophilic inflammation, and cytokine expression in an animal model of chronic airway inflammation. Guinea pigs were subjected to seven ovalbumin or saline exposures. The treatment with Y-27632 (1 mM) started at the fifth inhalation. Seventy-two hours after the seventh inhalation, the animals' pulmonary mechanics were evaluated, and exhaled nitric oxide (E-NO) was collected. The lungs were removed, and histological analysis was performed using morphometry. Treatment with Y-27632 in sensitized animals reduced E-NO concentrations, maximal responses of resistance, elastance of the respiratory system, eosinophil counts, collagen and elastic fiber contents, the numbers of cells positive for IL-2, IL-4, IL-5, IL-13, inducible nitric oxide synthase, matrix metalloproteinase-9, tissue inhibitor of metalloproteinase-1, transforming growth factor-beta, NF-kappa B, IFN-gamma, and 8-iso-prostaglandin F2 alpha contents compared with the untreated group (P < 0.05). We observed positive correlations among the functional responses and inflammation, remodeling, and oxidative stress pathway activation markers evaluated. In conclusion, Rho-kinase pathway activation contributes to the potentiation of the hyperresponsiveness, inflammation, the extracellular matrix remodeling process, and oxidative stress activation. These results suggest that Rho-kinase inhibitors represent potential pharmacological tools for the control of asthma.

Root niche separation can explain avoidance of seasonal drought stress and vulnerability of overstory trees to extended drought in a mature Amazonian forest

Large areas of Amazonian evergreen forest experience seasonal droughts extending for three or more months, yet show maximum rates of photosynthesis and evapotranspiration during dry intervals. This apparent resilience is belied by disproportionate mortality of the large trees in manipulations that reduce wet season rainfall, occurring after 2-3 years of treatment. The goal of this study is to characterize the mechanisms that produce these contrasting ecosystem responses. A mechanistic model is developed based on the ecohydrological framework of TIN (Triangulated Irregular Network)-based Real Time Integrated Basin Simulator + Vegetation Generator for Interactive Evolution (tRIBS+VEGGIE). The model is used to test the roles of deep roots and soil capillary flux to provide water to the forest during the dry season. Also examined is the importance of "root niche separation," in which roots of overstory trees extend to depth, where during the dry season they use water stored from wet season precipitation, while roots of understory trees are concentrated in shallow layers that access dry season precipitation directly. Observational data from the Tapajo's National Forest, Brazil, were used as meteorological forcing and provided comprehensive observational constraints on the model. Results strongly suggest that deep roots with root niche separation adaptations explain both the observed resilience during seasonal drought and the vulnerability of canopy-dominant trees to extended deficits of wet season rainfall. These mechanisms appear to provide an adaptive strategy that enhances productivity of the largest trees in the face of their disproportionate heat loads and water demand in the dry season. A sensitivity analysis exploring how wet season rainfall affects the stability of the rainforest system is presented. Citation: Ivanov, V. Y., L. R. Hutyra, S. C. Wofsy, J. W. Munger, S. R. Saleska, R. C. de Oliveira Jr., and P. B. de Camargo (2012), Root niche separation can explain avoidance of seasonal drought stress and vulnerability of overstory trees to extended drought in a mature Amazonian forest, Water Resour. Res., 48, W12507, doi:10.1029/2012WR011972.

Acute heat stress impairs performance parameters and induces mild intestinal enteritis in broiler chickens: Role of acute hypothalamic-pituitary-adrenal axis activation

Studies on the environmental consequences of stress are relevant for economic and animal welfare reasons. We recently reported that long-term heat stressors (31 +/- 1 degrees C and 36 +/- 1 degrees C for 10 h/d) applied to broiler chickens (Gallus gallus domesticus) from d 35 to 42 of life increased serum corticosterone concentrations, decreased performance variables and the macrophage oxidative burst, and produced mild, multifocal acute enteritis. Being cognizant of the relevance of acute heat stress on tropical and subtropical poultry production, we designed the current experiment to analyze, from a neuroimmune perspective, the effects of an acute heat stress (31 +/- 1 degrees C for 10 h on d 35 of life) on serum corticosterone, performance variables, intestinal histology, and peritoneal macrophage activity in chickens. We demonstrated that the acute heat stress increased serum corticosterone concentrations and mortality and decreased food intake, BW gain, and feed conversion (P < 0.05). We did not find changes in the relative weights of the spleen, thymus, and bursa of Fabricius (P > 0.05). Increases in the basal and the Staphylococcus aureus-induced macrophage oxidative bursts and a decrease in the percentage of macrophages performing phagocytosis were also observed. Finally, mild, multifocal acute enteritis, characterized by the increased presence of lymphocytes and plasmocytes within the lamina propria of the jejunum, was also observed. We found that the stress-induced hypothalamic-pituitary-adrenal axis activation was responsible for the negative effects observed on chicken performance and immune function as well as for the changes in the intestinal mucosa. The data presented here corroborate with those presented in other studies in the field of neuroimmunomodulation and open new avenues for the improvement of broiler chicken welfare and production performance.

Increased vascular contractility and oxidative stress in beta(2)-adrenoceptor knockout mice: the role of NADPH oxidase

Background/Aims: beta(2)-adrenoceptor (beta(2)-AR) activation induces smooth muscle relaxation and endothelium-derived nitric oxide (NO) release. However, whether endogenous basal beta(2)-AR activity controls vascular redox status and NO bioavailability is unclear. Thus, we aimed to evaluate vascular reactivity in mice lacking functional beta(2)-AR (beta 2KO), focusing on the role of NO and superoxide anion. Methods and Results: Isolated thoracic aortas from beta 2KO and wild-type mice (WT) were studied. beta 2KO aortas exhibited an enhanced contractile response to phenylephrine compared to WT. Endothelial removal and L-NAME incubation increased phenylephrine-induced contraction, abolishing the differences between beta 2KO and WT mice. Basal NO availability was reduced in aortas from beta 2KO mice. Incubation of beta 2KO aortas with superoxide dismutase or NADPH inhibitor apocynin restored the enhanced contractile response to phenylephrine to WT levels. beta 2KO aortas exhibited oxidative stress detected by enhanced dihydroethidium fluorescence, which was normalized by apocynin. Protein expression of eNOS was reduced, while p47(phox) expression was enhanced in beta 2KO aortas. Conclusions: The present results demonstrate for the first time that enhanced NADPH-derived superoxide anion production is associated with reduced NO bioavailability in aortas of beta 2KO mice. This study extends the knowledge of the relevance of the endogenous activity of beta(2)-AR to the maintenance of the vascular physiology. Copyright (C) 2012 S. Karger AG, Basel

Brain Pathways Involved in the Modulatory Effects of Noradrenaline in Lateral Septal Area on Cardiovascular Responses

We have previously reported that stimulation of alpha-1 adrenoceptors by noradrenaline (NA) injected into the lateral septal area (LSA) of anaesthetized rats causes pressor and bradycardic responses that are mediated by acute vasopressin release into the circulation through activation of the paraventricular nucleus (PVN). Although the PVN is the final structure of this pathway, the LSA has no direct connections with the PVN, suggesting that other structures may connect these areas. To address this issue, the present study employed c-Fos immunohistochemistry to investigate changes caused by NA microinjection into the LSA in neuronal activation in brain structures related to systemic vasopressin release. NA microinjected in the LSA caused pressor and bradycardic responses, which were blocked by intraseptal administration of alpha-1 adrenoceptor antagonist (WB4101, 10 nmol/200 nL) or systemic V-1 receptor antagonist (dTyr(CH2)5(Me)AVP, 50 mu g/kg). NA also increased c-Fos immunoreactivity in the prelimbic cortex (PL), infralimbic cortex (IL), dorsomedial periaqueductal gray (dmPAG), bed nucleus of the stria terminalis (BNST), PVN, and medial amygdala (MeA). No differences in the diagonal band of Broca, cingulate cortex, and dorsolateral periaqueductal gray (dlPAG) were found. Systemic administration of the vasopressin receptor antagonist dTyr AVP (CH2)5(Me) did not change the increase in c-Fos expression induced by intra-septal NA. This latter effect, however, was prevented by local injection of the alpha-1 adrenoceptor antagonist WB4101. These results suggest that areas such as the PL, IL, dmPAG, BNST, MeA, and PVN could be part of a circuit responsible for vasopressin release after activation of alpha-1 adrenoceptors in the LSA.

Ectopic expression of a fruit phytoene synthase from Citrus paradisi Macf. promotes abiotic stress tolerance in transgenic tobacco

Abscisic acid (ABA) is an important regulator of plant responses to environmental stresses and an absolute requirement for stress tolerance. Recently, a third phytoene synthase (PSY3) gene paralog was identified in monocots and demonstrated to play a specialized role in stress-induced ABA formation, thus suggesting that the first committed step in carotenogenesis is a key limiting step in ABA biosynthesis. To examine whether the ectopic expression of PSY, other than PSY3, would similarly affect ABA level and stress tolerance, we have produced transgenic tobacco containing a fruit-specific PSY (CpPSY) of grapefruit (Citrus paradisi Macf.). The transgenic plants contained a single- or double-locus insertion and expressed CpPSY at varying transcript levels. In comparison with the wild-type plants, the CpPSY expressing transgenic plants showed a significant increase on root length and shoot biomass under PEG-, NaCl- and mannitol-induced osmotic stress. The enhanced stress tolerance of transgenic plants was correlated with the increased endogenous ABA level and expression of stress-responsive genes, which in turn was correlated with the CpPSY copy number and expression level in different transgenic lines. Collectively, these results provide further evidence that PSY is a key enzyme regulating ABA biosynthesis and that the altered expression of other PSYs in transgenic plants may provide a similar function to that of the monocot's PSY3 in ABA biosynthesis and stress tolerance. The results also pave the way for further use of CpPSY, as well as other PSYs, as potential candidate genes for engineering tolerance to drought and salt stress in crop plants.

Chronic Stress Improves the Myocardial Function without Altering L-type Ca+2 Channel Activity in Rats

Background: Chronic stress is associated with cardiac remodeling; however the mechanisms have yet to be clarified. Objective: The purpose of this study was test the hypothesis that chronic stress promotes cardiac dysfunction associated to L-type calcium Ca2+ channel activity depression. Methods: Thirty-day-old male Wistar rats (70 - 100 g) were distributed into two groups: control (C) and chronic stress (St). The stress was consistently maintained at immobilization during 15 weeks, 5 times per week, 1h per day. The cardiac function was evaluated by left ventricular performance through echocardiography and by ventricular isolated papillary muscle. The myocardial papillary muscle activity was assessed at baseline conditions and with inotropic maneuvers such as: post-rest contraction and increases in extracellular Ca2+ concentration, in presence or absence of specific blockers L-type calcium channels. Results: The stress was characterized for adrenal glands hypertrophy, increase of systemic corticosterone level and arterial hypertension. The chronic stress provided left ventricular hypertrophy. The left ventricular and baseline myocardial function did not change with chronic stress. However, it improved the response of the papillary muscle in relation to positive inotropic stimulation. This function improvement was not associated with the L-type Ca2+ channel. Conclusion: Chronic stress produced cardiac hypertrophy; however, in the study of papillary muscle, the positive inotropic maneuvers potentiated cardiac function in stressed rats, without involvement of L-type Ca2+ channel. Thus, the responsible mechanisms remain unclear with respect to Ca2+ influx alterations. (Arq Bras Cardiol 2012;99(4):907-914)

Interaction between Advanced Glycation End Products Formation and Vascular Responses in Femoral and Coronary Arteries from Exercised Diabetic Rats

Background: The majority of studies have investigated the effect of exercise training (TR) on vascular responses in diabetic animals (DB), but none evaluated nitric oxide (NO) and advanced glycation end products (AGEs) formation associated with oxidant and antioxidant activities in femoral and coronary arteries from trained diabetic rats. Our hypothesis was that 8-week TR would alter AGEs levels in type 1 diabetic rats ameliorating vascular responsiveness. Methodology/Principal Findings: Male Wistar rats were divided into control sedentary (C/SD), sedentary diabetic (SD/DB), and trained diabetic (TR/DB). DB was induced by streptozotocin (i.p.: 60 mg/kg). TR was performed for 60 min per day, 5 days/week, during 8 weeks. Concentration-response curves to acetylcholine (ACh), sodium nitroprusside (SNP), phenylephrine (PHE) and tromboxane analog (U46619) were obtained. The protein expressions of eNOS, receptor for AGEs (RAGE), Cu/Zn-SOD and Mn-SOD were analyzed. Tissues NO production and reactive oxygen species (ROS) generation were evaluated. Plasma nitrate/nitrite (NOx-), superoxide dismutase (SOD), catalase (CAT), thiobarbituric acid reactive substances (TBARS) and N-epsilon-(carboxymethyl) lysine (CML, AGE biomarker). A rightward shift in the concentration-response curves to ACh was observed in femoral and coronary arteries from SD/DB that was accompanied by an increase in TBARS and CML levels. Decreased in the eNOS expression, tissues NO production and NOx- levels were associated with increased ROS generation. A positive interaction between the beneficial effect of TR on the relaxing responses to ACh and the reduction in TBARS and CML levels were observed without changing in antioxidant activities. The eNOS protein expression, tissues NO production and ROS generation were fully re-established in TR/DB, but plasma NOx- levels were partially restored. Conclusion: Shear stress induced by TR fully restores the eNOS/NO pathway in both preparations from non-treated diabetic rats, however, a massive production of AGEs still affecting relaxing responses possibly involving other endothelium-dependent vasodilator agents, mainly in coronary artery.

Inducible Nitric Oxide Synthase Inhibition Attenuates Physical Stress-Induced Lung Hyper-Responsiveness and Oxidative Stress in Animals with Lung Inflammation

Mechanisms involved in stress-induced asthmatic alterations have been poorly characterised. We assessed whether inducible nitric oxide synthase (iNOS) inhibition modulates the stress-amplified lung parenchyma responsiveness, oxidative stress and extracellular matrix remodelling that was previously increased by chronic lung inflammation. Guinea pigs were subjected to 7 exposures to ovalbumin (1-5 mg/ml) or saline (OVA and SAL groups) over 4 weeks. To induce behavioural stress, animals were subjected to a forced swimming protocol (5 times/week, over 2 weeks; SAL-Stress and OVA-Stress groups) 24 h after the 4th inhalation. 1400W (iNOS-specific inhibitor) was administered intraperitoneally in the last 4 days of the protocol (SAL-1400W, OVA-1400W, SAL-Stress+1400W and OVA-Stress+1400W groups). Seventy-two hours after the last inhalation, animals were anaesthetised and exsanguinated, and adrenal glands were removed. Lung tissue resistance and elastance were evaluated by oscillatory mechanics and submitted for histopathological evaluation. Stressed animals had higher adrenal weights compared to non-stressed groups, which were reduced by 1400W treatment. Behavioural stress in sensitised animals amplified the resistance and elastance responses after antigen challenge, numbers of eosinophils and iNOS+ cells, actin content and 8-iso-PGF2 alpha density in the distal lung compared to the OVA group. 1400W treatment in ovalbumin-exposed and stressed animals reduced lung mechanics, iNOS+ cell numbers and 8-iso-PGF2a density compared to sensitised and stressed animals that received vehicle treatment. We concluded that stress amplifies the distal lung constriction, eosinophilic inflammation, iNOS expression, actin content and oxidative stress previously induced by chronic lung inflammation. iNOS-derived NO contributes to stress-augmented lung tissue functional alterations in this animal model and is at least partially due to activation of the oxidative stress pathway. copyright (C) 2012S. Karger AG, Basel

Cannabidiol blocks long-lasting behavioral consequences of predator threat stress: Possible involvement of 5HT1A receptors

Posttraumatic stress disorder (PTSD) is an incapacitating syndrome that follows a traumatic experience. Predator exposure promotes long-lasting anxiogenic effect in rodents, an effect related to symptoms found in PTSD patients. Cannabidiol (CBD) is a non-psychotomimetic component of Cannabis sativa with anxiolytic effects. The present study investigated the anti-anxiety actions of CBD administration in a model of PTSD. Male Wistar rats exposed to a predator (cat) received, 1 h later, singled or repeated i.p. administration of vehicle or CBD. Seven days after the stress animals were submitted to the elevated plus maze. To investigate the involvement of 5HT1A receptors in CBD effects animals were pre-treated with WAY100635, a 5HT1A receptor antagonist. To explore possible neurobiological mechanisms involved in these effects, 5HT1A receptor mRNA and BDNF protein expression were measured in the hippocampus, frontal cortex, amygdaloid complex and dorsal periaqueductal gray. Repeated administration of CBD prevented long-lasting anxiogenic effects promoted by a single predator exposure. Pretreatment with WAY100635 attenuated CBD effects. Seven days after predator exposure 5HT1A mRNA expression was up regulated in the frontal cortex and hippocampus. CBD and paroxetine failed to prevent this effect. No change in BDNF expression was found. In conclusion, predator exposure promotes long-lasting up-regulation of 5HT1A receptor gene expression in the hippocampus and frontal cortex. Repeated CBD administration prevents the long-lasting anxiogenic effects observed after predator exposure probably by facilitating 5HT1A receptors neurotransmission. Our results suggest that CBD has beneficial potential for PTSD treatment and that 5HT1A receptors could be a therapeutic target in this disorder. (C) 2012 Elsevier Ltd. All rights reserved.