Conflict between Threat Sensitivity and Sensation Seeking in the Adolescent Brain : Role of the Hippocampus, and Neurobehavioural Plasticity Induced by Pleasurable Early Enriched Experience

Adolescence is characterized both by the exacerbation of the experience of anxiety, fear or threat, on one hand, and by increased reward seeking (reward sensitivity) and risk taking on the other hand. The rise of these apparently opposite processes, i.e., threat-related anxiety and reward-related sensation seeking, seems to stem from a relatively decreased top-down inhibition of amygdala and striatal circuits by regulatory systems (e.g., prefrontal cortex, hippocampus) that mature later. The present commentary article aims to discuss recent related literature and focusses on two main issues: (i) the septo-hippocampal system (in particular the ventral hippocampus) might be a crucial region for the regulation of approach-avoidance conflict and also for the selection of the most appropriate responses during adolescence, and (ii) developmental studies involving early-life pleasurable-enriched experience (as opposed to early-life adversity) might be a useful study paradigm in order to decipher whether neuroplasticity induced by such experiences (for example, in the hippocampus and associated circuitry) may lead to better top-down inhibition and more "balanced" adolescent responses to environmental demands

Modelos animales en psicopatología y psicofarmacología : del análisis experimental de la conducta a la neurogenética

En los primeros apartados del presente trabajo se consideran las diversas disciplinas que han motivado el desarrollo de los modelos animales, así como la aportación de éstos al progreso de las mismas. A continuación se exponen los criterios de validez predictiva, aparente, de constructo y convergente por los que se rige la validación de los modelos animales, al tiempo que se plantea la necesidad de considerar también un criterio de consistencia-fiabilidad en el uso e interpretación de los resultados experimentales, lo cual se ilustra con un ejemplo. Seguidamente, el contínuo progreso que experimentan los modelos animales en función del rápido avance científico en determinadas líneas de investigación se ilustra con la aparición y/o cambios de procedimiento de modelos de ansiedad, estrés o aprendizaje. Finalmente, se presenta una tabla resumen de los modelos animales más utilizados en el estudio de las principales psicopatologías y se comentan algunos modelos psicogenéticos, farmacogenéticos y neurogenéticosThe contributions of different scientific disciplines to the progress of the animal models, as well as the need of such models for the development of those areas, are considered in the first part of the present work. Criteria for validating animal models of human (normal and abnormal) behavior, such as predictive, face, construct and convergent validities, in addition to a new suggested criterion concerning the consistency/reliability in the use of the models and interpretation of the data, are discussed. In considering the progress of animal models, different examples regarding the development of certain analogues of anxiety, stress and learning are presented. Finally, the most used models for the main psychopatological categories are summarized in a table, and some psychogenetic, pharmacogenetic and neurogenetic models are commente

Acute Relaxation Response Induced by Tibetan Singing Bowl Sounds : A Randomized Controlled Trial

UDBELLATERRAThe prevalence of anxiety has increased dramatically due to COVID-19, so effective preventive interventions are welcome. The main objective of our study was to compare the acute relaxation response (RR) induced by Tibetan singing bowl (TSB) sound-based treatment against progressive muscle relaxation (PMR) and a control waiting list group (CWL) in a single treatment session in an adult nonclinical anxious population. In this cross-sectional randomized control trial, 50 participants selected based on high state anxiety were randomly assigned to one of the experimental groups. Pre/post self-reported anxiety, electroencephalographic activity (EEG), and heart rate variability (HRV) were recorded at baseline (T1), minute 15 (T2), minute 30 (T3), and minute 45 (T4). The TSB group showed significant reductions in alpha power (from T2 to T4) and increased HRV (from T3 to T4) compared with the PMR and CWL groups. Moreover, TSB and PMR both showed significant reductions in self-reported anxiety compared with CWL, with this effect being more evident in the TSB group. We concluded that a single session of TSB treatment was able to induce a more evident psychological/physiological relaxation response compared with PMR and CWL. TSB could be a relevant acute intervention in stressful situations or crisis intervention and while waiting for conventional interventions

Neonatal handling decreases unconditioned anxiety, conditioned fear, and improves two-way avoidance acquisition: a study with the inbred Roman high (RHA-I)- and low-avoidance (RLA-I) rats of both sexes

The present study evaluated the long-lasting effects of neonatal handling (H; administered during the first 21 days of life) on unlearned and learned anxiety-related responses in inbred Roman High- (RHA-I) and Low-avoidance (RLA-I) rats. To this aim, untreated and neonatally-handled RHA-I and RLA-I rats of both sexes were tested in the following tests/tasks in baseline acoustic startle (BAS) test, a context-conditioned fear (CCF) test and the acquisition of two-way active –shuttle box- avoidance (SHAV). RLA-I rats showed higher unconditioned (NOE, ZM, BAS) and conditioned (CCF, SHAV) anxiety. H treatment increased exploration of the novel object in the NOE test as well as exploration of the open sections of the ZM test in both rat strains and sexes, although the effects were relatively more marked in the (high anxious) RLA-I strain and in females. Neonatal handling did not affect BAS, but reduced context-conditioned fear in both strains and sexes, and improved shuttle box avoidance acquisition especially in RLA-I (and particularly in females) and in female RHA-I rats. These are completely novel findings, and may suggest that H-induced changes in hippocampal function, which is enhanced in RLA-Is vs RHA-I rats, could be a candidate mechanism underlying the observed long-lasting benefits of neonatal handling on known hippocampal-dependent responses/tasks

El tractament de l'ansietat amb bols tibetans : un enfocament complementari prometedor

Un nou estudi realitzat amb la col·laboració d'investigadors de l'Institut de Neurociències (INc-UAB) demostra que l'ús de bols tibetans és un enfocament prometedor per a reduir l'ansietat i les respostes a l'estrès. Aquests bols s'utilitzen des de fa segles a cerimònies meditatives al Tíbet i tenen un so relaxant únic.Un nuevo estudio realizado con la colaboración de investigadores del Institut de Neurociències (INc-UAB) demuestra que el uso de cuencos tibetanos es un enfoque prometedor para reducir la ansiedad y las respuestas al estrés. Estos cuencos se usan desde hace siglos en ceremonias meditativas en el Tíbet y tienen un sonido relajante único.A new study conducted with the collaboration of Institut de Neurociències (INc-UAB) researchers demonstrates that the use of Tibetan singing bowls is a promising approach for reducing anxiety and stress responses. These bowls have been used for centuries in meditative ceremonies in Tibet and have a unique relaxing sound

Effects of Tail Pinch on BDNF and trkB Expression in the Hippocampus of Roman Low- (RLA) and High-Avoidance (RHA) Rats

In this article, we describe the effects of tail pinch (TP), a mild acute stressor, on the levels of brain-derived neurotrophic factor (BDNF) and its tyrosine kinase receptor B (trkB) proteins in the hippocampus (HC) of the outbred Roman High- (RHA) and Low-Avoidance (RLA) rats, one of the most validated genetic models for the study of fear/anxiety- and stress-related behaviors. Using Western blot (WB) and immunohistochemistry assays, we show for the first time that TP induces distinct changes in the levels of BDNF and trkB proteins in the dorsal (dHC) and ventral (vHC) HC of RHA and RLA rats. The WB assays showed that TP increases BDNF and trkB levels in the dHC of both lines but induces opposite changes in the vHC, decreasing BDNF levels in RHA rats and trkB levels in RLA rats. These results suggest that TP may enhance plastic events in the dHC and hinder them in the vHC. Immunohistochemical assays, carried out in parallel to assess the location of changes revealed by the WB, showed that, in the dHC, TP increases BDNF-like immunoreactivity (LI) in the CA2 sector of the Ammon's horn of both Roman lines and in the CA3 sector of the Ammon's horn of RLA rats while, in the dentate gyrus (DG), TP increases trkB-LI in RHA rats. In contrast, in the vHC, TP elicits only a few changes, represented by decreases of BDNF- and trkB-LI in the CA1 sector of the Ammon's horn of RHA rats. These results support the view that the genotypic/phenotypic features of the experimental subjects influence the effects of an acute stressor, even as mild as TP, on the basal BDNF/trkB signaling, leading to different changes in the dorsal and ventral subdivisions of the HC

Contribution of the Roman rat lines/strains to personality neuroscience: neurobehavioral modeling of internalizing/externalizing psychopathologies

The Roman high-avoidance (RHA) and low-avoidance (RLA) rat lines/strains were established in Rome through bidirectional selection of Wistar rats for rapid (RHA) or extremely poor (RLA) acquisition of a two-way active avoidance task. Relative to RHAs, RLA rats exhibit enhanced threat sensitivity, anxiety, fear and vulnerability to stress, a passive coping style and increased sensitivity to frustration. Thus, RLA rats’ phenotypic profile falls well within the “internalizing” behavior spectrum. Compared with RLAs and other rat strains/stocks, RHAs present increased impulsivity and reward sensitivity, deficits in social behavior and attentional/cognitive processes, novelty-induced hyper-locomotion and vulnerability to psychostimulant sensitization and drug addiction. Thus, RHA rats’ phenotypes are consistent with a “disinhibiting externalizing” profile. Many neurobiological/molecular traits differentiate both rat lines/strains. For example, relative to RLA rats, RHAs exhibit decreased function of the prefrontal cortex (PFC), hippocampus and amygdala, increased functional tone of the mesolimbic dopamine system, a deficit of central metabotropic glutamate-2 (mGlu2) receptors, increased density of serotonin 5-HT2A receptors in the PFC, impairment of GABAergic transmission in the PFC, alterations of several synaptic markers and increased density of pyramidal immature dendrític spines in the PFC. These characteristics suggest an immature brain of RHA rats and are reminiscent of schizophrenia features like hypofrontality and disruption of the excitation/inhibition cortical balance. We review evidence supporting RLA rats as a valid model of anxiety/fear, stress and frustration vulnerability, whereas RHA rats represent a promising translational model of neurodevelopmental alterations related to impulsivity, schizophrenia-relevant features and comorbidity with drug addiction vulnerability

Effects of environmental and physiological covariates on sex differences in unconditioned and conditioned anxiety and fear in a large sample of genetically heterogeneous (N/Nih-HS) rats

Physiological and environmental variables, or covariates, can account for an important portion of the variability observed in behavioural/physiological results from different laboratories even when using the same type of animals and phenotyping procedures. We present the results of a behavioural study with a sample of 1456 genetically heterogeneous N/Nih-HS rats, including males and females, which are part of a larger genome-wide fine-mapping QTL (Quantitative Trait Loci) study. N/Nih-HS rats have been derived from 8 inbred strains and provide very small distance between genetic recombinations, which makes them a unique tool for fine-mapping QTL studies. The behavioural test battery comprised the elevated zero-maze test for anxiety, novel-cage (open-field like) activity, two-way active avoidance acquisition (related to conditioned anxiety) and context-conditioned freezing (i.e. classically conditioned fear). Using factorial analyses of variance (ANOVAs) we aimed to analyse sex differences in anxiety and fear in this N/Nih-HS rat sample, as well as to assess the effects of (and interactions with) other independent factors, such as batch, season, coat colour and experimenter. Body weight was taken as a quantitative covariate and analysed by covariance analysis (ANCOVA). Obliquely-rotated factor analyses were also performed separately for each sex, in order to evaluate associations among the most relevant variables from each behavioural test and the common dimensions (i.e. factors) underlying the different behavioural responses. ANOVA analyses showed a consistent pattern of sex effects, with females showing less signs of anxiety and fear than males across all tests. There were also significant main effects of batch, season, colour and experimenter on almost all behavioural variables, as well as "sex × batch", "sex × season" and "sex × experimenter" interactions. Body weight showed significant effects in the ANCOVAs of most behavioural measures, but sex effects were still present in spite of (and after controlling for) these "body weight" effects. Factor analyses of relevant variables from each test showed a two-fold factor structure in both sexes, with the first factor mainly representing anxiety and conditioned fear in males, while in females the first factor was dominated by loadings of activity measures. Thus, besides showing consistent sex differences in anxiety-, fear- and activity-related responses in N/Nih-HS rats, the present study shows that females' behaviour is predominantly influenced by activity while males are more influenced by anxiety. Moreover, the results point out that, besides "sex" effects, physiological variables such as colour and body weight, and environmental factors as batch/season or "experimenter", have to be taken into account in both behavioural and quantitative genetic studies because of their demonstrated influences on phenotypic outcomes

Ansietats normals i anormals : de la neurofarmacologia a la neurogenètica

Hem revisat els sistemes neuroreguladors centrals implicats en 1'ansietat, fent un èmfasi especial en aquell que tradicionalment s'hi ha considerat més relacionat, el sistema GABAèrgic. Es descriuen els principals moduladors de 1'acció GABAèrgica i es discuteix la importància de la composició molecular del complex GABAA/Bz/Cl- en determinar la seva resposta a les manipulations farmacolbgiques. A mes, es fa un resum dels diversos intents realitzats des de línies de recerca diferents per trobar possibles substàncies endògenes que actuïn als receptors benzodiazepinics. Pel que fa a altres sistemes de neuroregulació implicats en 1'ansietat, es revisen les evidencies a favor del paper de la serotonina, la colecistocinina, el factor d'alliberament de la corticotropina, el glutamat i el neuropèptid Y. Finalment es parla de 1'existència de diferències individuals en la susceptibilitat ansiosa i dels intents d'abordar-les mitjançant 1'estudi de la possible contribució genètica en soques de rosegadors que difereixen en la reactivitat emocional

PRACTICUM II de Psicologia Mèdica en els Centres d'Atenció Primària sobre la comunicació no verbal en la relació metge-pacient

La Unitat de Psicologia Mèdica de la Facultat de Medicina de la UAB va posar en marxa durant el curs 2005/2006 el Practicum II de Psicologia Mèdica en els Centres d'Atenció Primària amb l'objectiu que els estudiants comencin a copsar la importància de les conductes i dels estats psicològics de les persones en els processos de salut-malaltia que es veuen en els Centres d'Atenció Primària (CAP). El Practicum està dedicat específicament als aspectes no verbals de la comunicació entre el professional de la salut i el pacient. L'experiència forma part de l'assignatura "Bases Psicològiques dels Estats de Salut i de Malaltia", impartida a segon curs de Medicina; s'inscriu en el paradigma de l'aprenentatge des de la pràctica que protagonitzen els professionals del sistema sanitari; i s'emmarca en el context d'un procés impulsat pels equips deganals de la Facultat de Medicina de la UAB des del curs 2004/2005 per tal d'apropar l'estudiant a la pràctica clínica des del primer curs de carrera i avançar cap a la consecució dels objectius que marquen les directrius europees. Cada alumne realitza dues visites programades a un CAP i participa en quatre sessions de tutoria a la Facultat en grups reduïts. En les visites al CAP, ha d'assistir a sessions de consulta amb diversos professionals de l'àmbit de la salut. Ha d'observar, identificar i enregistrar els elements no verbals que es descriuen en els objectius del Practicum i el context en què ocorren. A les sessions de tutories s'entrena els alumnes per a fer les observacions mitjançant material audiovisual i es discuteixen les observacions realitzades en els CAP. A més, també s'utilitza com a material una monografia específica sobre el tema. L'experiència es valora favorablement. tant des del punt de vista dels resultats obtinguts pels alumnes com per la seva satisfacció.The Medical Psychology Unit of the UAB School of Medicine initiated during the academic year 2005/2006 the Medical Psychology Practicum II in primary care centers with the goal that students realize the importance of human behaviors and psychological states in health-illness processes in primary care centers. The Practicum is specifically oriented to non verbal communication between the health professional and the patient. The experience is part of the subject "Psychological Bases of Health and Illness", taught in second course of Medicine; it is registered "learning from the practice" paradigm that professionals from the health system lead; and it is framed in the context of a process promoted by the UAB School of Medicine Deanship since the academic year 2004/2005 with the goal of bringing the clinical practice to the student from the first academic year and advancing towards the achievement of the goals that the European guidelines mark. Each student does two programmed visits to primary health center and participates in four tutorials of reduced groups in the Faculty. During the visits to the primary health center, he has to attend sessions of consultation with professionals from several health areas. He has to observe, to identify and to record the non verbal elements that are described in the Practicum goals and the context in which they occur. At the tutorials, students are trained to observe through audiovisual didactic material and the observations carried out at the primary health center are argued. Moreover, a specific monograph is also used as a specific material about the subject. The experience of these last two years has been satisfactory so for the professionals of the primary care centres as for the tutors and the students. The experience is valued favorably considering students' academic results and their satisfaction