Distinct fos-expressing neuronal ensembles in the ventromedial prefrontal cortex mediate food reward and extinction memories

In operant learning, initial reward-associated memories are thought to be distinct from subsequent extinction-associated memories. Memories formed during operant learning are thought to be stored in “neuronal ensembles.” Thus, we hypothesize that different neuronal ensembles encode reward- and extinction-associated memories. Here, we examined prefrontal cortex neuronal ensembles involved in the recall of reward and extinction memories of food self-administration.Wefirst trained rats to lever press for palatable food pellets for 7 d (1 h/d) and then exposed them to 0, 2, or 7 daily extinction sessions in which lever presses were not reinforced. Twenty-four hours after the last training or extinction session, we exposed the rats to either a short 15 min extinction test session or left them in their homecage (a control condition). We found maximal Fos (a neuronal activity marker) immunoreactivity in the ventral medial prefrontal cortex of rats that previously received 2 extinction sessions, suggesting that neuronal ensembles in this area encode extinction memories. We then used the Daun02 inactivation procedure to selectively disrupt ventral medial prefrontal cortex neuronal ensembles that were activated during the 15 min extinction session following 0 (no extinction) or 2 prior extinction sessions to determine the effects of inactivating the putative food reward and extinction ensembles, respectively, on subsequent nonreinforced food seeking 2 d later. Inactivation of the food reward ensembles decreased food seeking, whereas inactivation of the extinction ensembles increased food seeking. Our results indicate that distinct neuronal ensembles encoding operant reward and extinction memories intermingle within the same cortical area

Spatial and temporal dynamics of the abundance of crustose calcareous algae on the southernmost coral reefs of the western Atlantic (Abrolhos Bank, Brazil)

Crustose calcareous algae (CCA) constitute one of the main reef builders on the Abrolhos Bank, Brazil. Once CCA taxonomy is locally understood, differences in growth-forms may be useful for the delimitation of taxa using characteristics such as the presence or absence of surface protuberances. Here, growth-forms were used to identify and quantify the most common CCA taxa on the shallow reefs (3-10 m) of the Abrolhos Bank to determine possible changes in the CCA community over a period of 10 years, and the ecological significance of CCA to local reefs was interpreted. The CCA assemblages were surveyed from 2006-2015 by using fixed photoquadrats at four sites in the inner (10-20 km from the mainland) and mid-shelf reefs (40-75 km from the mainland). The five most common CCA taxa were Pneophyllum conicum, the Lithophyllum kaiserii / Lithophyllum sp. complex, Melyvonnea erubescens, the Hydrolithon boergesenii / Porolithon onkodes complex and Peyssonelia sp. The overall mean CCA cover on the reefs was 20%. A comparison with a previous monitoring study in the same region indicated that the CCA cover nearly doubled from 2003-2008 to 2006-2015. This study reveals that the coral-killing species P. conicum dominated CCA flora on the shallow Abrolhos reefs in the last decade, and the local specific abundance of CCA slightly fluctuated over time and was species-and site-specific. The information obtained in this study contributes to the understanding of the ecology of the key calcifying components of the Abrolhos reefs and provides a useful baseline for exploring the responses of CCA to future environmental changes.PELDMudancas Climaticas scientific programmes of the Brazilian National Science Agency (CNPq)Brazilian IODP Program (CAPES/MEC)P&D Program ANP/BrasoilFAPERJDiretoria Pesquisa Cient, Inst Pesquisas, Jardim Bot Rio De Janeiro, Rua Pacheco Leao 915, BR-22460030 Rio De Janeiro, RJ, BrazilUniv Fed Rio de Janeiro, Inst Biol, BR-21941599 Rio De Janeiro, RJ, BrazilUniv Fed Espirito Santo, Dept Oceanog, Ave Fernando Ferrari 514, BR-29090600 Vitoria, ES, BrazilUniv Fed Sao Paulo, Inst Mar, Campus Baixada Santista, BR-11030400 Santos, SP, BrazilUniv Fed Paraiba, Ctr Ciencias Aplicadas & Educ, Campus 4 Litoral Norte, BR-58297000 Rio Tinto, PB, BrazilUniv Fed Sao Paulo, Inst Mar, Campus Baixada Santista, BR-11030400 Santos, SP, BrazilANP/Brasoil: 48610.011015/2014-55Web of Scienc

Rationale, study design, and analysis plan of the Alveolar Recruitment for ARDS Trial (ART): Study protocol for a randomized controlled trial

Background: Acute respiratory distress syndrome (ARDS) is associated with high in-hospital mortality. Alveolar recruitment followed by ventilation at optimal titrated PEEP may reduce ventilator-induced lung injury and improve oxygenation in patients with ARDS, but the effects on mortality and other clinical outcomes remain unknown. This article reports the rationale, study design, and analysis plan of the Alveolar Recruitment for ARDS Trial (ART). Methods/Design: ART is a pragmatic, multicenter, randomized (concealed), controlled trial, which aims to determine if maximum stepwise alveolar recruitment associated with PEEP titration is able to increase 28-day survival in patients with ARDS compared to conventional treatment (ARDSNet strategy). We will enroll adult patients with ARDS of less than 72 h duration. The intervention group will receive an alveolar recruitment maneuver, with stepwise increases of PEEP achieving 45 cmH(2)O and peak pressure of 60 cmH2O, followed by ventilation with optimal PEEP titrated according to the static compliance of the respiratory system. In the control group, mechanical ventilation will follow a conventional protocol (ARDSNet). In both groups, we will use controlled volume mode with low tidal volumes (4 to 6 mL/kg of predicted body weight) and targeting plateau pressure <= 30 cmH2O. The primary outcome is 28-day survival, and the secondary outcomes are: length of ICU stay; length of hospital stay; pneumothorax requiring chest tube during first 7 days; barotrauma during first 7 days; mechanical ventilation-free days from days 1 to 28; ICU, in-hospital, and 6-month survival. ART is an event-guided trial planned to last until 520 events (deaths within 28 days) are observed. These events allow detection of a hazard ratio of 0.75, with 90% power and two-tailed type I error of 5%. All analysis will follow the intention-to-treat principle. Discussion: If the ART strategy with maximum recruitment and PEEP titration improves 28-day survival, this will represent a notable advance to the care of ARDS patients. Conversely, if the ART strategy is similar or inferior to the current evidence-based strategy (ARDSNet), this should also change current practice as many institutions routinely employ recruitment maneuvers and set PEEP levels according to some titration method.Hospital do Coracao (HCor) as part of the Program 'Hospitais de Excelencia a Servico do SUS (PROADI-SUS)'Brazilian Ministry of Healt

Exposure to acute restraint stress reinstates nicotine-induced place preference in rats

Tobacco addiction is associated with high rates of relapse to drug use even after prolonged periods of abstinence. Relapse can occur upon reexposure to the drug of abuse, exposure to stress or to stimuli associated with drug consumption. The reinstatement of conditioning place preference (CPP) provides a simple and easy approach to investigate the mechanisms for drug relapse. We evaluated whether exposure to restraint stress could reinstate nicotine-induced CPP 1 or 15 days after its extinction. Nicotine produced place preference to the compartment paired with its injections during conditioning (0.16 mg/kg, subcutaneous; four drug sessions). Once established, nicotine CPP was extinguished by alternate exposure to each compartment after a saline injection (four exposures to each compartment). After this extinction phase, the reinstatement of place conditioning was investigated. For this purpose, rats were exposed to 30-min restraint stress 1 or 15 days after the extinction test, then immediately tested for reinstatement of CPP. Our results show that exposure to restraint stress reinstated CPP 1 and 15 days after extinction. Our study indicates for the first time that the vulnerability to stress-induced reinstatement of nicotine CPP is long-lasting, corroborating clinical studies showing that stress is positively associated with relapse to tobacco use even after along period of nicotine withdrawal. Behavioural Pharmacology 20:109-113 (C) 2009 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins.Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP

Behavioral and neuroendocrine effects of the exposure to chronic restraint or variable stress in early adolescent rats

Stress events during adolescence may contribute to the expression or exacerbation of physical and behavioral disorders. However, little attention has been given to the physiological and behavioral changes promoted by stress during this period of ontogeny. In the present study we investigated, in adolescent male rats, the effects of repeated exposure to restraint or variable stress on: (a) locomotor activity and corticosterone levels after exposure to a novel environment; (b) corticosterone levels in response to the exposure to restraint stress; and (c) changes in body, thymus and adrenal weights. The results demonstrated that repeated exposure to restraint or variable stress reduced the locomotor response, but did not affect corticosterone secretion, in response to a novel environment. Moreover, both chronic stress procedures did not change corticosterone secretion in response to acute restraint stress. Furthermore, our results showed that repeated restraint, but not variable stress, produced a decrease in body weight along the stress exposure. Finally, we observed that the exposure to variable stress reduced the thymus relative weight. Taken together our results suggest that behavioral and physiological changes induced by exposure to chronic stress during adolescence depend on the stress regimen. (C) 2011 ISDN. Published by Elsevier Ltd. All rights reserved.Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP

Stress-induced reinstatement of amphetamine-conditioned place preference and changes in tyrosine hydroxylase in the nucleus accumbens in adolescent rats

Drug abuse among humans often begins during adolescence. Exposure to psychostimulants during this age period may have long-term consequences which can render the organism more susceptible to drug abuse and relapse later in life. It has been demonstrated that exposure to stress can promote relapse to drug use even after long periods of withdrawal. The reinstatement of conditioned place preference (CPP) is a useful animal model for studying relapse. In humans and animals, changes in tyrosine hydroxylase (TN) have been related to drug addiction. Our study examined whether amphetamine-induced CPP during adolescence could be reinstated by exposure to stress 1 (adolescence) and 30 (adulthood) days after the extinction test. We also investigated TH levels following the reinstatement of CPP. Our results showed that amphetamine-induced CPP during adolescence can be reinstated by stress exposure 1 day (P42, end of adolescence) but not 30 days after extinction (P71, adulthood). Moreover the reinstatement of AMPH-induced CPP by stress exposure occurred in the presence of decreased TH in the nucleus accumbens. In conclusion, our data add new evidence that neuroadaptations on TH may mediate relapse to drug-seeking behavior induced by stress within adolescence. (C) 2010 Elsevier B.V. All rights reserved.Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES

Influence of the single or combined administration of cocaine and testosterone in autonomic and neuroendocrine responses to acute restraint stress

Abuse of cocaine and androgenic-anabolic steroids (AASs) has become a serious public health problem. Despite reports of an increase in the incidence of simultaneous abuse of these substances, potential toxic interactions between cocaine and AASs are poorly known. In the present study, we investigated the effects of either single or combined administration of testosterone and cocaine for one or 10 consecutive days on autonomic (arterial pressure, heart rate and tail cutaneous temperature) and neuroendocrine (plasma corticosterone) responses induced by acute restraint stress in rats. Combined administration of testosterone and cocaine for 10 days reduced the increase in heart rate and plasma corticosterone level, as well as the fall in tail skin temperature induced by restraint stress. Furthermore, repeated administration of cocaine inhibited the increase in arterial pressure observed during restraint, and this effect was not affected by coadministration of testosterone. Ten-day combined administration of testosterone and cocaine increased basal values of arterial pressure. Moreover, chronic administration of testosterone induced rest bradycardia and elevated basal level of plasma corticosterone. One-day single or combined administration of the drugs did not affect any parameter investigated. In conclusion, the present study demonstrated that combined administration of testosterone and cocaine changed the autonomic and neuroendocrine responses to acute restraint stress. These findings suggest that interaction between AASs and cocaine may affect the ability to cope with stressful events.Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq

Cardiovascular Complications following Chronic Treatment with Cocaine and Testosterone in Adolescent Rats

Concomitant use of anabolic androgenic steroids and cocaine has increased in the last years. However, the effects of chronic exposure to these substances during adolescence on cardiovascular function are unknown. Here, we investigated the effects of treatment for 10 consecutive days with testosterone and cocaine alone or in combination on basal cardiovascular parameters, baroreflex activity, hemodynamic responses to vasoactive agents, and cardiac morphology in adolescent rats. Administration of testosterone alone increased arterial pressure, reduced heart rate (HR), and exacerbated the tachycardiac baroreflex response. Cocaine-treated animals showed resting bradycardia without changes in arterial pressure and baroreflex activity. Combined treatment with testosterone and cocaine did not affect baseline arterial pressure and HR, but reduced baroreflex-mediated tachycardia. None of the treatments affected arterial pressure response to either vasoconstrictor or vasodilator agents. Also, heart to body ratio and left and right ventricular wall thickness were not modified by drug treatments. However, histological analysis of left ventricular sections of animals subjected to treatment with testosterone and cocaine alone and combined showed a greater spacing between cardiac muscle fibers, dilated blood vessels, and fibrosis. These data show important cardiovascular changes following treatment with testosterone in adolescent rats. However, the results suggest that exposure to cocaine alone or combined with testosterone during adolescence minimally affect cardiovascular function.Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP

Effect of the Single or Combined Administration of Cocaine and Testosterone on Cardiovascular Function and Baroreflex Activity in Unanesthetized Rats

Abuse of cocaine and androgenic-anabolic steroids has become a serious public health problem. Despite reports of an increase in the incidence of simultaneous illicit use of these substances, potential toxic interactions between cocaine and androgenic-anabolic steroids in the cardiovascular system are unknown. In the present study, we investigated the effect of single or combined administration of testosterone and cocaine for 1 or 10 consecutive days on basal cardiovascular parameters, baroreflex activity, and hemodynamic responses to vasoactive agents in unanesthetized rats. Ten-day combined administration of testosterone and cocaine increased baseline arterial pressure. Changes in arterial pressure were associated with altered baroreflex activity and impairment of both hypotensive response to intravenous sodium nitroprusside and pressor effect of intravenous phenylephrine. Chronic single administration of either testosterone or cocaine did not affect baseline arterial pressure. However, testosterone-treated animals presented rest bradycardia, cardiac hypertrophy, alterations in baroreflex activity, and enhanced response to sodium nitroprusside. Repeated administration of cocaine affected baroreflex activity and impaired vascular responsiveness to both sodium nitroprusside and phenylephrine. One-day single or combined administration of the drugs did not affect any parameter investigated. In conclusion, the present results suggest a potential interaction between toxic effects of cocaine and testosterone on the cardiovascular activity. Changes in baseline arterial pressure after combined administration of these 2 drugs may result from alterations in baroreflex activity and impairment of vascular responsiveness to vasoactive agents.Fundacao de Amparo a Pesquisa do Estado de Sao Paulo [2010/16192-8]Fundacao de Amparo a Pesquisa do Estado de Sao PauloConselho Nacional de Desenvolvimento Cientifico e Tecnologico [474177/2010-6]Conselho Nacional de Desenvolvimento Cientifico e TecnologicoPrograma de Apoio ao Desenvolvimento Cientifico da Faculdade de Ciencias FarmaceuticasPrograma de Apoio ao Desenvolvimento Cientifico da Faculdade de Ciencias FarmaceuticasFundacao para Desenvolvimento da UNESPFundacao para Desenvolvimento da UNES