Dopamine release induced by atypical antipsychotics in prefrontal cortex requires 5-HT1A receptors but not 5-HT2A receptors

Atypical antipsychotic drugs (APDs) increase dopamine (DA) release in prefrontal cortex (PFC), an effect probably mediated by the direct or indirect activation of the 5-HT1A receptor (5-HT1AR). Given the very low in-vitro affinity of most APDs for 5-HT1ARs and the large co-expression of 5-HT1ARs and 5-HT2A receptors (5-HT2ARs) in the PFC, this effect might result from the imbalance of 5-HT1AR and 5-HT2AR activation after blockade of these receptors by APDs, for which they show high affinity. Here we tested this hypothesis by examining the dependence of the APD-induced DA release in medial PFC (mPFC) on each receptor by using in-vivo microdialysis in wild-type (WT) and 5-HT1AR and 5-HT2AR knockout (KO) mice. Local APDs (clozapine, olanzapine, risperidone) administered by reverse dialysis induced a dose-dependent increase in mPFC DA output equally in WT and 5-HT2AR KO mice whereas the DA increase was absent in 5-HT1AR KO mice. To examine the relative contribution of both receptors to the clozapine-induced DA release in rat mPFC, we silenced G-protein-coupled receptors (GPCRs) in vivo with N-ethoxycarbonyl-2-ethoxy-1,2-dihydroquinoline (EEDQ) while 5-HT 1ARs or 5-HT2A/2CRs in the mPFC were selectively protected with the respective antagonists WAY-100635 or ritanserin. The inactivation of GPCRs while preserving ∼70% of 5-HT2A/2CRs prevented the clozapine-induced DA rise in mPFC. In contrast, clozapine increased DA in mPFC of EEDQ-treated rats whose 5-HT1ARs were protected (∼50% of control rats). These results indicate that (1) 5-HT1ARs are necessary for the APDs-induced elevation in cortical DA transmission, and (2) this effect does not require 5-HT2AR blockade by APDs. © 2010 CINP.This work was supported by grants SAF 2007-62378 and SENY Fundació. A. B. is recipient of a Ramón y Cajal contract from MICINN-IDIBAPS. M. M. is a recipient of a predoctoral fellowship from CSIC (I3P program).Peer Reviewe

Dopamine Release Induced by Atypical Antipsychotics in Prefrontal Cortex Requires 5-HT(1A) Receptors but Not 5-HT(2A) Receptors

Atypical antipsychotic drugs (APDs) increase dopamine (DA) release in prefrontal cortex (PFC), an effect probably mediated by the direct or indirect activation of the 5-HT(1A) receptor (5-HT(1A)R). Given the very low in-vitro affinity of most APDs for 5-HT(1A)Rs and the large co-expression of 5-HT(1A)Rs and 5-HT(2A) receptors (5-HT(2A)Rs) in the PFC, this effect might result from the imbalance of 5-HT(1A)R and 5-HT(2A)R activation after blockade of these receptors by APDs, for which they show high affinity. Here we tested this hypothesis by examining the dependence of the APD-induced DA release in medial PFC (mPFC) on each receptor by using in-vivo microdialysis in wild-type (WT) and 5-HT(1A)R and 5-HT(2A)R knockout (KO) mice. Local APDs (clozapine, olanzapine, risperidone) administered by reverse dialysis induced a dose-dependent increase in mPFC DA output equally in WT and 5-HT(2A)R KO mice whereas the DA increase was absent in 5-HT(1A)R KO mice. To examine the relative contribution of both receptors to the clozapine-induced DA release in rat mPFC, we silenced G-protein-coupled receptors (GPCRs) in vivo with N-ethoxycarbonyl-2-ethoxy-1,2-dihydroquinoline (EEDQ) while 5-HT(1A)Rs or 5-HT(2A)/2CRs in the mPFC were selectively protected with the respective antagonists WAY-100635 or ritanserin. The inactivation of GPCRs while preserving ∼70% of 5-HT(2A)/(2C)Rs prevented the clozapine-induced DA rise in mPFC. In contrast, clozapine increased DA in mPFC of EEDQ-treated rats whose 5-HT(1A)Rs were protected (∼50% of control rats). These results indicate that (1) 5-HT(1A)Rs are necessary for the APDs-induced elevation in cortical DA transmission, and (2) this effect does not require 5-HT(2A)R blockade by APDs

Papel de la calidad de la grasa de la dieta sobre los niveles postprandiales de secretina, colecistoquinina y polipéptido pancreático en humanos

The effects of adaptation to two diets differing in the type of dietary fat on the circulating levels of secretin, cholecystokinin, and pancreatic polypeptide, were investigated in humans. A relationship with the results concerning gastric acid secretion and gastrin release previously described by us, was also examined. The study in volved 18 cholecystectomized subjects previously submitted to a 30-day adaptation period to diets containing olive (group O) or sunflower oil (group S) as the main fat source. During the experimental period, physiological stimulation was achieved by ingestion of 200 mL oleic acid- (group O) or linoleic acid enriched (group S) liquid mixed meals. Food ingestion did not induce no significant changes in plasma secretin concentration in any of the groups, and no signijicant differences were observed between them for basal and postprandial situations. Plasma cholecystokinin le veIs were signijicantly higher in group O throughout the 30-120 min postprandial periodo The type of dietary fat affected the pancreatic polypeptide response to food, since values in group O were significantly higher than in group S at any point during the postprandial period, thus, despite of significant release in both grollps after the meal. lt is suggested that endogenous cholecystokinin may be responsible for the attenuated gastric acid secretory response and the suppression of serum gastrin previously observed in the subjects of group O, through a somatostatin-mediated (paracrine) or peptide YY-mediated (endocrine) mechanism. Secretin does not seem to be in volved in the fat-induced inhibition of human gastric acid secretion, and a role for pancreatic polypeptide is doubtful.Los efectos de la adaptación a dos dietas que diferían en el tipo de grasa, sobre los niveles circulantes de secretina, colecistoquinina y polipéptido pancreático fueron investigados en humanos. También fue examinada la relación, previamente descrita por nosotros, con los resultados que concernían a la secreción de ácido gástrico y la liberación de gastrina. El estudio incluyó a 18 sujetos colecistectomizados previamente sometidos a un período de adaptación de 30 días a dietas que contenían aceite de oliva (grupo O) o de girasol (grupo G) como fuente de grasa principal. Durante el periodo experimental, la estimulación fisiológica se consiguió mediante la ingestión de 200 mi de ácido oleico (grupo O) o aceite de girasol (grupo S) mezclados con la comida. La ingestión de la dieta no indujo cambios significativos sobre la concentración en plasma de secretina en ninguno de los dos grupos, tampoco fueron observadas diferencias significativas entre dicha concentración plasmática en situaciones basal y postprandial. Los niveles plasmáticos de colecistoquinina fueron significativamente mayores en el grupo O durante un periodo postprandial de 30-120 minutos. El tipo de grasa de la dieta afectó a la respuesta del polipéptido pancreático a la comida, los valores en el grupo O fueron significativamente mayores a los del grupo S en cualquier punto durante el período postprandial, a pesar de la significativa liberación en ambos grupos tras la comida. Se sugirió que la colecistoquinina endógena podría ser responsable de la atenuación de la repuesta secetora de ácido gástrico y de la supresión de la serina sérica previamente observada en los sujetos del grupo O, a través dee un mecanismo mediado por somatostatina (paracrino) o por péptido YY (endocrino). La secretina no parece estar implicada en la inhibición inducida por la grasa de la secreción gástrica en humanos, y es dudoso el papel atribuido al polipéptido pancreático

Red en cultura material prehistórica: talleres de experimentación lítica en titulaciones de la UA

Una parte muy importante de las herramientas que fueron elaborando los seres humanos a lo largo de más de 2,5 millones de años se fabricaron durante la Prehistoria usando diferentes tipos de rocas. Entre los contenidos curriculares de los grados en Historia en España y en másteres afines, destacan diversas nociones sobre tecnología e instrumental lítico prehistórico, para que el alumnado conozca los procesos de producción lítica tallada, su evolución tecnológica y tipológica, y los procesos de clasificación y análisis. A pesar del creciente empleo de material gráfico como recurso docente, la metodología de clase teórica/participativa se muestra insuficiente a la hora de conseguir buenos resultados de aprendizaje. El desarrollo de talleres de experimentación lítica tallada sobre instrumental prehistórico permite el aprendizaje mediante la interacción y una mejor asimilación por parte de los estudiantes. La experiencia de las asignaturas del Grado en Historia y del Máster en Arqueología Profesional y Gestión del Patrimonio de la UA es un ejemplo de evaluación de las fortalezas y debilidades del desarrollo de dichos talleres

Effects of management regimes on structure, composition and diversity of seasonally inundated herbaceous communities in the Mkomazi National Park, Tanzania

The effects of management regimes on structural composition and diversity of seasonally inundated herbaceous communities were investigated in the Mkomazi National Park, Tanzania. Three sites were selected based on management regimes, that is "fire-grazing" (FG), "fire-no grazing" (FNG) and "no fire-no grazing" (NFNG), and sampled in the 2015 wet season. The studied vegetation parameters resulted significantly different across the sites, with the exceptions of species abundance between NFNG versus FG and NFNG versus FNG sites and species evenness, which remained constant among sites. A significantly higher species richness, Shannon diversity Index, standing biomass and percentage vegetation cover was detected at FNG site, than in the other sites. No significant differences arose when comparing FG and NFNG sites. Although the responses we found may in part be caused by confounding underlying variables such as variation in soil type, soil moisture or elevation, the patterns found may contribute to a more general understanding of the effects of management regimes in seasonally inundated savannah, as well as to sound approaches in environmental conservation and management. However, further research is needed to support our findings, replicating the study in other areas under the same or similar management conditions and in a wider array of ecosystems. 2018 John Wiley & Sons Ltd

Fear expression is suppressed by tyrosine administration

Animal studies have demonstrated that catecholamines regulate several aspects of fear conditioning. In humans, however, pharmacological manipulations of the catecholaminergic system have been scarce, and their primary focus has been to interfering with catecholaminergic activity after fear acquisition or expression had taken place, using L-Dopa, primarily, as catecholaminergic precursor. Here, we sought to determine if putative increases in presynaptic dopamine and norepinephrine by tyrosine administered before conditioning could affect fear expression. Electrodermal activity (EDA) of 46 healthy participants (24 placebo, 22 tyrosine) was measured in a fear instructed task. Results showed that tyrosine abolished fear expression compared to placebo. Importantly, tyrosine did not affect EDA responses to the aversive stimulus (UCS) or alter participants' mood. Therefore, the effect of tyrosine on fear expression cannot be attributed to these factors. Taken together, these findings provide evidence that the catecholaminergic system influences fear expression in humans

Effectiveness of a strategy that uses educational games to implement clinical practice guidelines among Spanish residents of family and community medicine (e-EDUCAGUIA project):A clinical trial by clusters

This study was funded by the Fondo de Investigaciones Sanitarias FIS Grant Number PI11/0477 ISCIII.-REDISSEC Proyecto RD12/0001/0012 AND FEDER Funding.Background: Clinical practice guidelines (CPGs) have been developed with the aim of helping health professionals, patients, and caregivers make decisions about their health care, using the best available evidence. In many cases, incorporation of these recommendations into clinical practice also implies a need for changes in routine clinical practice. Using educational games as a strategy for implementing recommendations among health professionals has been demonstrated to be effective in some studies; however, evidence is still scarce. The primary objective of this study is to assess the effectiveness of a teaching strategy for the implementation of CPGs using educational games (e-learning EDUCAGUIA) to improve knowledge and skills related to clinical decision-making by residents in family medicine. The primary objective will be evaluated at 1 and 6months after the intervention. The secondary objectives are to identify barriers and facilitators for the use of guidelines by residents of family medicine and to describe the educational strategies used by Spanish teaching units of family and community medicine to encourage implementation of CPGs. Methods/design: We propose a multicenter clinical trial with randomized allocation by clusters of family and community medicine teaching units in Spain. The sample size will be 394 residents (197 in each group), with the teaching units as the randomization unit and the residents comprising the analysis unit. For the intervention, both groups will receive an initial 1-h session on clinical practice guideline use and the usual dissemination strategy by e-mail. The intervention group (e-learning EDUCAGUIA) strategy will consist of educational games with hypothetical clinical scenarios in a virtual environment. The primary outcome will be the score obtained by the residents on evaluation questionnaires for each clinical practice guideline. Other included variables will be the sociodemographic and training variables of the residents and the teaching unit characteristics. The statistical analysis will consist of a descriptive analysis of variables and a baseline comparison of both groups. For the primary outcome analysis, an average score comparison of hypothetical scenario questionnaires between the EDUCAGUIA intervention group and the control group will be performed at 1 and 6months post-intervention, using 95% confidence intervals. A linear multilevel regression will be used to adjust the model. Discussion: The identification of effective teaching strategies will facilitate the incorporation of available knowledge into clinical practice that could eventually improve patient outcomes. The inclusion of information technologies as teaching tools permits greater learning autonomy and allows deeper instructor participation in the monitoring and supervision of residents. The long-term impact of this strategy is unknown; however, because it is aimed at professionals undergoing training and it addresses prevalent health problems, a small effect can be of great relevance. Trial registration: ClinicalTrials.gov: NCT02210442.Publisher PDFPeer reviewe

Passive smoking in babies: The BIBE study (Brief Intervention in babies. Effectiveness)

Background: There is evidence that exposure to passive smoking in general, and in babies in particular, is an important cause of morbimortality. Passive smoking is related to an increased risk of pediatric diseases such as sudden death syndrome, acute respiratory diseases, worsening of asthma, acute-chronic middle ear disease and slowing of lung growth. The objective of this article is to describe the BIBE study protocol. The BIBE study aims to determine the effectiveness of a brief intervention within the context of Primary Care, directed to mothers and fathers that smoke, in order to reduce the exposure of babies to passive smoking (ETS). Methods/Design: Cluster randomized field trial (control and intervention group), multicentric and open. Subject: Fathers and/or mothers who are smokers and their babies (under 18 months) that attend pediatric services in Primary Care in Catalonia. The measurements will be taken at three points in time, in each of the fathers and/or mothers who respond to a questionnaire regarding their baby's clinical background and characteristics of the baby's exposure, together with variables related to the parents' tobacco consumption. A hair sample of the baby will be taken at the beginning of the study and at six months after the initial visit (biological determination of nicotine). The intervention group will apply a brief intervention in passive smoking after specific training and the control group will apply the habitual care. Discussion: Exposure to ETS is an avoidable factor related to infant morbimortality. Interventions to reduce exposure to ETS in babies are potentially beneficial for their health. The BIBE study evaluates an intervention to reduce exposure to ETS that takes advantage of pediatric visits. Interventions in the form of advice, conducted by pediatric professionals, are an excellent opportunity for prevention and protection of infants against the harmful effects of ETS

From genetics to epigenetics: new perpectives in Tourette Syndrome research

Gilles de la Tourette Syndrome (TS) is a neurodevelopmental disorder marked by the appearance of multiple involuntary motor and vocal tics. TS presents high comorbidity rates with other disorders such as attention deficit hyperactivity disorder (ADHD) and obsessive compulsive disorder (OCD). TS is highly heritable and has a complex polygenic background. However, environmental factors also play a role in the manifestation of symptoms. Different epigenetic mechanisms may represent the link between these two causalities. Epigenetic regulation has been shown to have an impact in the development of many neuropsychiatric disorders, however very little is known about its effects on Tourette Syndrome.This review provides a summary of the recent findings in the genetic background of TS, followed by an overview on different epigenetic mechanisms, such as DNA methylation, histone modifications and non-coding RNAs in the regulation of gene expression. Epigenetic studies in other neurological and psychiatric disorders are discussed along with the TS-related epigenetic findings available in the literature to date. Moreover, we are proposing that some general epigenetic mechanisms seen in other neuropsychiatric disorders may also play a role in the pathogenesis of TS