Evidence for Phosphorylation-Dependent, Dynamic, Regulation of mGlu5 and Homer2 in Expression of Cocaine Aversion in Mice.

Cocaine-induced changes in the expression of the glutamate-related scaffolding protein Homer2 influence this drug's psychostimulant and rewarding properties. In response to neuronal activity, Homer2 is phosphorylated on S117/S216 by calcium-calmodulin kinase IIα (CaMKIIα), which induces a rapid dissociation of mGlu5-Homer2 scaffolds. Herein, we examined the requirement for Homer2 phosphorylation in cocaine-induced changes in mGlu5-Homer2 coupling, to include behavioral sensitivity to cocaine. For this, mice with alanine point mutations at (S117/216)-Homer2 (Homer2AA/AA ) were generated, and we determined their affective, cognitive and sensorimotor phenotypes, as well as cocaine-induced changes in conditioned reward and motor hyperactivity. The Homer2AA/AA mutation prevented activity-dependent phosphorylation of S216 Homer2 in cortical neurons, but Homer2AA/AA mice did not differ from wild-type (WT) controls with respect to Morris maze performance, acoustic startle, spontaneous or cocaine-induced locomotion. Homer2AA/AA mice exhibited signs of hypoanxiety similar to the phenotype of transgenic mice with a deficit in signal-regulated mGluR5 phosphorylation (Grm5AA/AA ). However, opposite of Grm5AA/AA mice, Homer2AA/AA mice were less sensitive to the aversive properties of high-dose cocaine under both place-conditioning and taste-conditioning procedures. Acute injection with cocaine caused dissociation of mGluR5 and Homer2 in striatal lysates from WT, but not Homer2AA/AA mice, suggesting a molecular basis for the deficit in cocaine aversion. These findings indicate that CaMKIIα-dependent phosphorylation of Homer2 gates the negative motivational valence of high-dose cocaine via regulation of mGlu5 binding, furthering an important role for dynamic changes in mGlu5-Homer interactions in addiction vulnerability.

Licentîa hypomnema: reflections and perceptions in teacher education / Licentîa hypomnema: reflexões e percepções na formação de educadoras(es) / Licentîa hypomnema: reflexiones y percepciones en la formación del profesorado

Student protagonism is paramount in the knowledge construction process. In this paper, we discuss a didactic-pedagogical resource called licentîa hypomnema (LH), inspired in portfolios and learning diaries in which student-teachers record their understandings and reflections regarding pedagogical topics learned at University in a meta-learning process on learning about teaching. The initial context of the research was a Psychological Development and Teaching course, offered in the Teacher Education program at Universidade de Brasília (UnB). Two of the authors, then Literacy and Languages Teaching students, produced their LH and peer assessed each other during the course. In their annotations, the student-authors recorded two pedagogical situations related to the use of LH in their own teaching practices, causing an impact on their formative path. These materials consist of the data for analysis and discussion. Moreover, we discuss possible uses of reflexive writing in teacher education and other learning contexts. Producing a LH supports knowledge production and allows students to connect theory and practice, which consequently influences the student's teaching practice. Since LH is a didactic-pedagogical resource and not a close-ended tool, both the context and individuals who use it should be considered.(AU)

O protagonismo de estudantes tem grande importância no processo de construção do conhecimento. Neste artigo, discutimos um recurso didático-pedagógico chamado licentîa hypomnema (LH), inspirado em portfólios e diários de aprendizagem, isto é, estudantes de licenciatura escrevem suas compreensões e reflexões acerca de assuntos pedagógicos vistos na universidade em um processo de meta-aprendizagem sobre aprender a ensinar. O contexto inicial da pesquisa foi um curso de Desenvolvimento Psicológico e Ensino, ministrado em cursos de Licenciatura da Universidade de Brasília (UnB). Duas das autoras eram estudantes do curso de Letras, elas produziram seus LH, realizando avaliação por pares entre si durante o curso. As estudantes-autoras trouxeram em seus registros duas situações pedagógicas relacionadas ao uso desse recurso em suas próprias práticas de ensino que causaram um impacto em suas trajetórias formativas. São esses relatos que compõem os dados para análise e discussão. Além disso, procuramos discutir possíveis desdobramentos para o uso do recurso da escrita reflexiva na formação docente e em outros contextos de aprendizagem. A produção do LH fornece suporte para a produção de conhecimento e permite ao aluno conectar teoria e prática, o que, consequentemente, reverbera na prática de ensino do aluno. O LH é um recurso didático-pedagógico e não uma ferramenta fechada, portanto, tanto o contexto quanto as pessoas que o utilizam devem ser considerados.(AU)

El protagonismo de los estudiantes tiene gran importancia en el proceso de construcción del conocimiento. En este trabajo, discutimos un recurso didáctico-pedagógico llamado licentîa hypomnema (LH), que se inspira en diarios de aprendizaje, es decir, estudiantes de profesorado escriben sus comprensiones y reflexiones sobre temas pedagógicos aprendidos en la universidad, produciendo un proceso de meta-aprendizaje sobre aprender a enseñar. El contexto inicial de la investigación fue un curso de Desarrollo Psicológico y Enseñanza, impartido en el programa de Formación de Profesores de la Universidade de Brasília (UnB). Dos de las autoras eran alumnas de la carrera de Letras que produjeron sus LH y realizaron una evaluación por pares mutua durante el curso. Las estudiantes autoras plantearon en su LH dos situaciones pedagógicas relacionadas con el uso de este recurso en sus propias prácticas de enseñanza, causando un impacto en su trayectoria formativa. Estos materiales constituyen los datos para el análisis y la discusión en esta investigación. Buscamos discutir posibles desdoblamientos para el uso del recurso de la escritura reflexiva en la formación docente y en otros contextos de aprendizaje. La producción de este recurso da soporte a la producción de conocimiento y permite al estudiante conectar teoría y práctica, lo que consecuentemente repercute en su práctica docente. El LH es un recurso didáctico-pedagógico y no una herramienta cerrada, por lo tanto, se debe considerar tanto el contexto como las personas que lo utilizan.(AU)

Teorías y modelos sobre los estilos de aprendizaje / Theories and models on learning styles

Introducción: diagnosticar la forma en que los alumnos aprenden, resulta necesario para el éxito del proceso formativo, pero las teorías y modelos relacionados con los estilos de aprendizaje resultan muy variados y se dificulta su aplicación. Objetivo: analizar diferentes teorías y modelos relativos a los estilos de aprendizaje desde una visión holística. Métodos: la búsqueda se desarrolló en español e inglés durante los últimos cuatro meses de 2021, se emplearon las bases de datos: Latindex, Redib, Redalyc, Ebsco, SciELO, Hinari, ISI Web y Scopus. Las palabras clave empleadas fueron: estilos de aprendizaje, modelo, características, metodologías, estrategias. Los criterios de selección se aplicaron a 811 fuentes bibliográficas identificadas inicialmente y fueron seleccionados 26 artículos. Desarrollo: se confrontaron diversos posicionamientos y experiencias desde los años 50 del siglo XX hasta la actualidad. Abordar diferentes enfoques de los estilos de aprendizaje arroja una perspectiva evolutiva de dicho fenómeno. El análisis holístico posibilita visualizar las implicaciones de los estilos de aprendizaje en el proceso enseñanza aprendizaje. Conclusiones: la integración de los modelos de Kolb y Honey y Mumford constituye una opción viable para su aplicación a la realidad educativa y posibilita un diagnóstico confiable para el proceso instructivo.

Introduction: the diagnosis of the way in which students learn is necessary for the success of the training process, but the theories and models related to learning styles are very varied, making their application difficult. Objective: to analyze different theories and models related to learning styles from a holistic view. Methods: The search was carried out in Spanish and English during the last four months of 2021, using the databases: Latindex, Redib, Redalyc, Ebsco, SciELO, Hinari, ISI Web, and Scopus. The keywords used were learning styles, model, characteristics, methodologies, strategies. The selection criteria were applied to 811 initially identified bibliographic sources, leaving 26 selected articles. Development: different positions and experiences were confronted from the 50's of the 20th centuries to the present. The approach of different approaches about learning styles throws an evolutionary perspective of this phenomenon. Holistic analysis makes it possible to visualize the implications of learning styles in the teaching-learning process. Conclusions: the integration of Kolb's models as well as Honey and Mumford constitute a viable option for its application to the educational reality, allowing a reliable diagnosis for the instructional process.

Importance of Perception of Errors and Challenges for Improving Psychological Conditioning: Mediating Effect of Expectancy-Value Using the Phantom Model for Taekwondo Athletes.

Maintenance of positive psychological conditioning can be a key factor in eliciting high human performance. In particular, perception of error forms a causal relationship with challenges regarding task performance. Therefore, this study aimed to investigate the mediation effect of expectancy value in the relationship between the perception of error and challenge using the Phantom Model through quantitative research. This study analyzed the causal relationship between perception of error, expectancy value, and challenge in 423 young Taekwondo athletes. Frequency analysis, confirmatory factor analysis, correlation analysis, and structural equation modeling were performed on the collected data using Jamovi 1.0.1 and AMOS 23.0 statistical programs to verify the hypothesis. The challenge demonstrated a significant difference in relation to the perception of error. These results demonstrated that the perception of error not only directly affected one's challenge but also explained the increased challenge by mediating expectations for success and subjective values. Hence, the positive perception of error increased the athletes' expectancy value and challenge.

Pills and prayers: a comparative qualitative study of community conceptualisations of pre-eclampsia and pluralistic care in Ethiopia, Haiti and Zimbabwe.

BACKGROUND: Pre-eclampsia is a leading cause of preventable maternal and perinatal deaths globally. While health inequities remain stark, removing financial or structural barriers to care does not necessarily improve uptake of life-saving treatment. Building on existing literature elaborating the sociocultural contexts that shape behaviours around pregnancy and childbirth can identify nuanced influences relating to pre-eclampsia care. METHODS: We conducted a cross-cultural comparative study exploring lived experiences and understanding of pre-eclampsia in Ethiopia, Haiti and Zimbabwe. Our primary objective was to examine what local understandings of pre-eclampsia might be shared between these three under-resourced settings despite their considerable sociocultural differences. Between August 2018 and January 2020, we conducted 89 in-depth interviews with individuals and 17 focus group discussions (n = 106). We purposively sampled perinatal women, survivors of pre-eclampsia, families of deceased women, partners, older male and female decision-makers, traditional birth attendants, religious and traditional healers, community health workers and facility-based health professionals. Template analysis was conducted to facilitate cross-country comparison drawing on Social Learning Theory and the Health Belief Model. RESULTS: Survivors of pre-eclampsia spoke of their uncertainty regarding symptoms and diagnosis. A lack of shared language challenged coherence in interpretations of illness related to pre-eclampsia. Across settings, raised blood pressure in pregnancy was often attributed to psychosocial distress and dietary factors, and eclampsia linked to spiritual manifestations. Pluralistic care was driven by attribution of causes, social norms and expectations relating to alternative care and trust in biomedicine across all three settings. Divergence across the contexts centred around nuances in religious or traditional practices relating to maternal health and pregnancy. CONCLUSIONS: Engaging faith and traditional caregivers and the wider community offers opportunities to move towards coherent conceptualisations of pre-eclampsia, and hence greater access to potentially life-saving care.

Effect of Chaihu-jia-Longgu-Muli decoction on withdrawal symptoms in rats with methamphetamine-induced conditioned place preference.

Traditional Chinese medicine detoxification prescription Chaihu-jia-Longgu-Muli decoction (CLMD) relieves depressive symptoms in patients withdrawing from methamphetamine. In the present study, we assessed the effects of CLMD on methamphetamine withdrawal in rats. A methamphetamine-intoxicated rat model was established. Rats were randomly divided into the control, model, high-dosage, medium-dosage, and low-dosage groups, receiving high, medium, and low doses of CLMD, respectively. Weekly body weight measurements revealed that rats treated with methamphetamine had the lowest body weight. The conditioned place preference (CPP) experiment revealed that methamphetamine-intoxicated rats stayed significantly longer in the drug-paired chamber than the control rats. However, after administering high-dosage CLMD, the amount of time the rats spent in the drug-paired chamber was significantly less than that of the model rats. Our open-field test revealed that the model group had lower crossing and rearing scores than the control group. Additionally, rats that received CLMD treatment exhibited higher crossing and rearing scores than the model rats. Striatal dopamine (DA), 5-hydroxytryptamine (5-HT), and endorphins (ß-EP) and serum interleukin (IL)-1α and IL-2 concentrations were estimated. Rats in the model group had lower striatal DA, 5-HT, and ß-EP and higher serum IL-1α and IL-2 concentrations than those in the control group. High-dosage CLMD administration significantly changed the concentrations of these molecules, such that they approached normal concentrations. In general, CLMD could prevent the development of methamphetamine-induced withdrawal symptoms in rats by increasing the DA, 5-HT, and ß-EP and lowering the IL-1α and IL-2 concentrations.

La dependencia emocional: un problema de la psicología y otras ciencias humanísticas / Emotional dependence: a problem in psychology and other humanistic sciences

RESUMEN Introducción: se consideran las ideas de L.S. Vygotsky (1896-1934) teórico del enfoque histórico-cultural con su propuesta para elaborar una teoría y práctica psicológica materialista-dialéctica. Objetivo: valorar la dependencia emocional con sus causas y factores asociados a partir de la apreciación teórica de los autores sobre su diagnóstico, orientación, educación, prevención, tratamiento y rehabilitación. Métodos: se realizó una revisión bibliográfica sobre la dependencia emocional por las bases de datos SciELO y Google Académico con predominio de los últimos 5 años, con la mirada multicausal, multidisciplinar, eminentemente psicológica, integracionista de la psicología cubana y de la escuela histórico-cultural de Vygotsky, consecuentes con lo psicobiológico, socio-económico-cultural en interacción con lo cualitativo-cuantitativo y lo clínico-epidemiológico. Desarrollo: se referenciaron múltiples disciplinas de las ciencias humanísticas, con el liderazgo de la psicología y el axioma vigotskiano: "...más allá de las potencialidades humanas para adaptarse al medio, están las posibilidades transformadoras del ser humano"; se reconocieron herramientas instrumentadas, devenidas en procesos psicológicos, protectores de personas con dependencia emocional. Conclusiones: la prevención de la dependencia emocional y su control, valorada a través de la escuela vigotskiana se apoya en la estimulación de la zona de desarrollo próximo y en la explicación de la situación social del desarrollo, regulada por actividades socio-culturales con su base natural en el sistema nervioso, regida por órganos funcionales, sin trasmisión biológica, con implicaciones de la psiconeuroinmunología, a partir de la cual se trata de solucionar el dilema cuerpo-mente relacionado con el tema.

ABSTRACT Introduction: the ideas of L.S. Vygotsky (1896-1934) theorist of the historical-cultural approach with his proposal to elaborate a materialist-dialectic psychological theory and practice are considered. Objective: to assess emotional dependence with its causes and associated factors based on the theoretical appreciation of the authors about its diagnosis, orientation, education, prevention, treatment and rehabilitation. Methods: a bibliographic review on emotional dependence was carried out by the SciELO and Google scholar databases with a predominance of the last 5 years, with a multicausal, multidisciplinary, eminently psychological, integrationist view of Cuban psychology and the historical-cultural school of Vygotsky, consistent with the psychobiological, socio-economic-cultural in interaction with the qualitative-quantitative and the clinical-epidemiological. Development: multiple disciplines of the humanistic sciences were referenced, with the leadership of psychology and the Vigotskian axiom: "... beyond the human potentialities to adapt to the environment, there are the transforming possibilities of the human being"; Instrumented tools were recognized, turned into psychological processes, protectors of people with emotional dependence. Conclusions: the prevention of emotional dependence and its control is valued through the Vigotskian school which is based on the stimulation of the zone of proximal development and on the explanation of the social situation of development, regulated by socio-cultural activities with its natural base in the nervous system, that is governed by functional organs, without biological transmission, with implications of psychoneuroimmunology, from which it is a matter of solving the mind-body dilemma related to the subject.

Stress-induced impairment of fear extinction recall is associated with changes in neuronal activity patterns in PVT.

Treatment resistance of anxiety-related disorders often arises from an inappropriate fear expression, impairment in fear extinction, and spontaneous return of fear. Stress exposure is considered a high risk factor for neuropsychiatric disorders, but understanding of the long-term consequences of stress is limited, particularly when it comes to treatment outcome. Therefore, studying the consequences of acute stress would provide critical information on the role of stress in psychopathology. In the present study, we investigated the effect of acute immobilization stress on anxiety-like behavior and on conditioned fear memory. Our results demonstrate that prior stress exposure had no effect on anxiety-related behavior, fear acquisition, as well as fear extinction compared to non-stressed controls, but resulted in significantly higher rates of freezing during recall of extinction, indicating a consolidation failure. Further, immunohistochemical analysis of the expression of the immediate early gene c-Fos after recall of extinction revealed increased neuronal activity in the posterior paraventricular nucleus of the thalamus (PVT) in previously stressed animals compared to non-stressed controls. These results indicate, firstly, that acute stress affects long-term fear memory even after successful extinction training, and secondly, a strong involvement of the PVT in maladaptive fear responses induced by prior stress. Thus, stress-induced changes in PVT neuronal activity might be of importance for the pathophysiology of stress-sensitive anxiety-related psychiatric disorders, since exposure to an earlier acute stressor could counteract the success of therapy.

Pre-Exposure, But Not Overshadowing, Inhibits Nocebo Hyperalgesia.

Nocebo hyperalgesia is a pervasive problem that significantly adds to the burden of pain. Conditioning is a key mechanism of nocebo hyperalgesia and recent evidence indicates that, once established, nocebo hyperalgesia is resistant to extinction. This means that preventive strategies are critical. We therefore tested whether two novel strategies - overshadowing (Experiment 1) and pre-exposure (Experiment 2) - could inhibit conditioned nocebo hyperalgesia. Overshadowing involves introducing additional cues during conditioning that should compete with and overshadow learning about the target nocebo cue. Pre-exposure involves pre-exposing the target nocebo cue in the absence of pain, which should diminish its ability to become associated with pain later. In both studies, healthy volunteers (N = 141) received exposure to a series of electrocutaneous pain stimuli with and without a sham electrode 'activated', which they were led to believe was a genuine hyperalgesic treatment. Nocebo conditioning was achieved by pairing sham activation with high pain prior to testing at equivalent pain intensity. In both studies, standard nocebo conditioning led to clear nocebo hyperalgesia relative to natural history controls. In Experiment 1, there was no evidence that overshadowing attenuated nocebo hyperalgesia. Importantly, however, Experiment 2 found that pre-exposure successfully attenuated nocebo hyperalgesia with post hoc analysis suggesting that this effect was dose-dependent. These findings provide novel evidence that pre-exposure, but not overshadowing, could be a cheap and effective way for mitigating the substantial harm caused by conditioned nocebo hyperalgesia in clinical settings. PERSPECTIVE: Nocebo hyperalgesia causes substantial patient burden with few preventive options available. Our study found novel evidence that pre-exposing treatment cues without pain, but not overshadowing them with other cues, has the capacity to inhibit conditioned nocebo hyperalgesia. Pre-exposure may therefore be an effective preventive strategy to combat nocebo hyperalgesia.

The Role of the Thalamus in Post-Traumatic Stress Disorder.

Post-traumatic stress disorder (PTSD) has a high lifetime prevalence and is one of the more serious challenges in mental health care. Fear-conditioned learning involving the amygdala has been thought to be one of the main causative factors; however, recent studies have reported abnormalities in the thalamus of PTSD patients, which may explain the mechanism of interventions such as eye movement desensitization and reprocessing (EMDR). Therefore, I conducted a miniature literature review on the potential contribution of the thalamus to the pathogenesis of PTSD and the validation of therapeutic approaches. As a result, we noticed the importance of the retinotectal pathway (superior colliculus-pulvinar-amygdala connection) and discussed therapeutic indicators.

Effects of Yuanhu- Zhitong tablets on alcohol-induced conditioned place preference in mice.

OBJECTIVES: This study aimed at determining the synergistic effects of Yuanhu Zhitong tablets (YHZTP) on alcohol-induced conditioned place preference (CPP) in mice, in addition, the intervention mechanism was preliminarily explored based on traditional Chinese Medicine (TCM) network pharmacology on alcohol addiction. METHODS: Alcohol-induced CPP mice were used to evaluate the effects of either YHZTP or levo-tetrahydropalmatine (l-THP) plus imperatorin (IMP) administration on animal behavior. The network pharmacological strategy was used to establish the "compound-target" and "disease-drug-target" network. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were performed on the shared targets between the compound and the disease. Twelve algorithms on CytoHubba were used to find the hub genes that were verified by qPCR. RESULTS: Systemic administration (2 g/kg, i.p.) of ethanol (EtOH) to mice was used to induce CPP. YHZTP On its own did not induce CPP or conditioned place aversion (CPA) at the doses of 0.3 g/kg or 0.6 g/kg (i.g.), but attenuated the acquisition and expression of EtOH-induce CPP in mice. In addition, YHZTP (0.3 or 0.6 g/kg) did not exhibit any effect on the motor activity of mice. Acquisition of alcohol-induced CPP was blocked by a combination of l-THP (5 mg/kg, i.g.) + IMP (2.5 mg/kg, i.g.) or l-THP (10 mg/kg, i.g.) + IMP (5 mg/kg, i.g.). However, the combination of l-THP (2.5 mg/kg, i.g.) + IMP (1.25 mg/kg, i.g.) or mono-administration of l-THP and IMP did not exhibit any effect on alcohol-induced CPP. YHZTP was also shown to reverse the up-regulation of Gabra1, Ptgs2, Mapk1, Mapk8, Mapk14, Nr3c, Prkca and Sirt1 genes and the down-regulation of Hhtr2a and Drd2 genes in the prefrontal cortex of EtOH induced CPP mice. These genes were associated with neuroactive ligand-receptor interactions, activation of the sphingolipid, calcium, cAMP, ErbB, NF-kappa B and MAPK signaling pathways. CONCLUSION: YHZTP inhibits EtOH-induced CPP behavior in mice while a combination of l-THP and IMP exerts a synergistic effect on the reduction of EtOH-induced CPP. Possible pharmacological mechanisms include inhibition of the expression of inflammatory factors and regulation of neurotransmitter receptor levels. Therefore, YHZTP is a novel candidate for the treatment of alcohol addiction.

Effects of processed Aconiti tuber on the extinction and reinstatement of morphine-induced conditioned place preference in rats.

AIM OF THE STUDY: To investigate the effect of processed Aconiti tuber (PAT) administered during or after the time of conditioned place preference (CPP) training on the extinction and reinstatement of morphine-priming CPP in rats. The dynorphin level in rats' nucleus accumbens (NAc) is detected as a target of the Dynorphin/Kappa Opioid Receptor (KOR) system for the possible mechanism. MATERIALS AND METHODS: Eight groups of rats were subcutaneously (s.c.) injected with morphine (10mg/kg) (on days 2,4,6,8) or saline (1ml/kg) (on days 3,5,7,9) alternately for 8 days. Five groups, including groups (Mor + Water, Mor + PAT (1.0/3.0g/kg) (S) and Sal + PAT(1.0/3.0g/kg)), were orally given distilled water or PAT 1.0 or 3.0 g/kg daily on days 1-8 during CPP training while other three groups, including groups (Sal + Water and Mor + PAT (1.0/3.0g/kg)(P), were given distilled water or PAT daily from day 10 until CPP was extinct. Morphine 1mg/kg (s.c.) was used to reinstate the extinct CPP and the CPP scores were recorded. The dynorphin concentration in nucleus accumbens (NAc) was assayed by radioimmunoassay after the last CPP measurement. RESULTS: 1) The CPP extinction shortened in Mor + PAT (1.0/3.0 g/kg) (S) groups but extended in Mor + PAT (1.0/3.0 g/kg)(P) groups. 2) Morphine-priming CPP did not change either in Mor + PAT (1.0/3.0 g/kg) (S) or Mor + PAT (1.0/3.0 g/kg)(P) groups. 3) The dynorphin concentration in NAc increased either in Mor + PAT (1.0/3.0 g/kg)(S) or Mor + PAT (1.0/3.0 g/kg)(P) groups. CONCLUSIONS: 1) PAT shortened the extinction from morphine induced CPP when administrated before CPP acquisition, whereas it extended the extinction when administrated after CPP formation. 2) PAT administrated during or after CPP training did not affect morphine-priming reinstatement of morphine induced CPP. 3) Dynorphin/KOR system might be a target to regulate morphine-induced CPP extinction but not reinstatement.

Conditioned place aversion of caustic paste and hot-iron disbudding in dairy calves.

Cauterization by hot iron and application of caustic paste are 2 common methods of disbudding calves. In this study, we compared the affective experience of these 2 procedures on young dairy calves using conditioned place aversion. Male dairy calves (n = 14; 7 ± 2 d old) were disbudded by both thermal and chemical methods (1 horn bud at a time, 48 h apart). Calves received treatments in pens made visually distinct with either red squares or blue triangles on the walls. Calves were restricted to these treatment pens for 6 h following disbudding. For all treatments, calves received a sedative (xylazine, 0.2 mg/kg), local anesthetic (lidocaine, 5 mL), and analgesic (meloxicam, 0.5 mg/kg). Calves were then tested for conditioned place aversion at 48, 72, and 96 h after their last treatment. During tests, calves were placed in a neutral pen connected to both treatment pens where they had previously been disbudded. Time spent in each treatment pen was recorded until calves chose to lie down for 1 min (latency to lie down: 31.0 ± 8.6 min). During the first test (48 h after last disbudding), calves spent more time in the pen associated with hot-iron disbudding compared with what would be expected by chance (intercept: 73.5%, 95% CI: 56.5, 90.5) and fewer calves lay down in the caustic paste pen than in the hot-iron pen (3 vs. 10 lying events). No evidence of preference for the hot-iron pen was found in the following test sessions (72 and 96 h since last disbudding). These results suggest that calves initially remember caustic paste disbudding as a more negative experience than hot-iron disbudding, even with the use of sedation, local anesthesia, and analgesia.

Inhaled Lavandula angustifolia essential oil enhances extinction learning and inhibits memory updating in mice submitted to the contextual fear conditioning.

ETHNOPHARMACOLOGICAL RELEVANCE: Lavender (Lavandula angustifolia) essential oil (EO) has a long history of use in emotional illness, including anxiety disorders. Cognitive mechanisms of learning and memory play a pivotal role in the etiology and maintenance of anxiety since exposure to cues related to aversive situations induces high arousal and anticipatory anxiety. Memory become labile after its reactivation and can be modulated by reconsolidation or extinction. Inhibition of memory reconsolidation or facilitation of memory extinction may be effective in preventing or minimizing the effect of contextual cues on anticipatory anxiety. AIM OF THE STUDY: We investigated the effect of Lavandula angustifolia EO in the memory updating of conditioned contextual fear. MATERIALS AND METHODS: Adult male C57Bl6 mice were submitted to fear conditioning. Two days after conditioning the mice underwent a reactivation session in a hybrid context and were then immediately exposed to vaporized water or essential oil at concentrations of 1%, 2.5% or 5% for 3 h. Two days later, the mice were tested in the original or an altered context and their freezing behavior was measured. In addition, mice were subjected to a fear memory recovery protocol followed by a reinstatement session. RESULTS: In the contextual fear test, 1% essential oil, but not 2.5% or 5%, reduced the freezing behavior response, whereas after a reinstatement session, exposure to 1% essential oil increased the freezing behavior response. CONCLUSIONS: These results suggest that Lavandula angustifolia essential oil enhances memory extinction and, consequently, inhibits memory updating.

Prior Therapeutic Experiences, Not Expectation Ratings, Predict Placebo Effects: An Experimental Study in Chronic Pain and Healthy Participants.

INTRODUCTION: Many clinical trials fail because of placebo responses. Prior therapeutic experiences and patients' expectations may affect the capacity to respond to placebos in chronic disorders. OBJECTIVE: The scope of this study in 763 chronic orofacial pain and healthy study participants was to compare the magnitude and prevalence of placebo effects and determine the putative role of prior therapeutic experiences vs. expectations. METHODS: We tested placebo propensity in a laboratory setting by using 2 distinct levels of individually tailored painful stimulations (high pain and low pain) to reinforce expectations and provide a hypoalgesic experience (conditioning phase). Afterwards, both levels of pain were surreptitiously set at a moderate pain level to test for placebo effects (testing phase). Pain and expectation ratings were assessed as primary outcomes using visual analog scales. RESULTS: In both chronic pain and healthy participants, placebo effects were similar in magnitude, with the larger prevalence of responders in the healthy participants. Although chronic pain participants reported higher pain relief expectations, expectations did not account for the occurrence of placebo effects. Rather, prior experience via conditioning strength mediated placebo effects in both pain and healthy participants. CONCLUSIONS: These findings indicate that participants with chronic pain conditions display robust placebo effects that are not mediated by expectations but are instead directly linked to prior therapeutic experiences. This confirms the importance of assessing the therapeutic history while raising questions about the utility of expectation ratings. Future research is needed to enhance prediction of responses to placebos, which will ultimately improve clinical trial designs.

Approach Behavior Induced by 10.6-µm Laser Stimulation at Acupoint ST36 in a Rat Model of Incisional Pain.

Objective: Laser stimulation (LS) at both the injury site and specific acupoints may induce analgesic effects. The purpose of this study is to investigate the effects of LS at injury site or acupoint on analgesic-associated approach behavior and determine whether opioid receptors in the anterior cingulate cortex (ACC) were involved. Methods: The left hindpaw incision was established in rats. LS (10.6 µm) was performed at the ipsilateral (left) acupoint ST36 (Zusanli) or locally to the incision site. Characteristic guarding pain behavior was measured to assess incision-induced pain. A two-chamber conditioned place preference (CPP) paradigm was used to measure approach behavior induced by pain relief. To inhibit opioid receptors, naloxone was microinjected into the ACC before LS. Results: A delayed analgesic effect (24 h after treatment) was induced in both the LS groups (ST36 and incision site) as compared with the sham control or model groups (p < 0.05). An immediate (30 min after the end of the LS) decrease in guarding pain (p < 0.001) and CPP for the LS chamber (p < 0.001) were observed only in the ST36 LS group. The administration of naloxone in ACC inhibited the LS-induced analgesic effect and CPP (p < 0.05). Conclusions: Our results highlight the novel approach behavior of pain relief induced by 10.6-µm LS at ST36 in a rat model of incisional pain, and implicate ACC opioid receptor signaling in these actions.

Fear Learning Enhances Prefrontal Cortical Suppression of Auditory Thalamic Inputs to the Amygdala in Adults, but Not Adolescents.

Adolescence is characterized by increased susceptibility to the development of fear- and anxiety-related disorders. Adolescents also show elevated fear responding and aversive learning that is resistant to behavioral interventions, which may be related to alterations in the circuitry supporting fear learning. These features are linked to ongoing adolescent development of medial prefrontal cortical (PFC) inputs to the basolateral amygdala (BLA) that regulate neural activity and contribute to the refinement of fear responses. Here, we tested the hypothesis that the extent of PFC inhibition of the BLA following fear learning is greater in adults than in adolescents, using anesthetized in vivo recordings to measure local field potentials (LFPs) evoked by stimulation of PFC or auditory thalamic (MgN) inputs to BLA. We found that BLA LFPs evoked by stimulation of MgN inputs were enhanced in adults following fear conditioning. Fear conditioning also led to reduced summation of BLA LFPs evoked in response to PFC train stimulation, and increased the capacity of PFC inhibition of MgN inputs in adults. These data suggest that fear conditioning recruits additional inhibitory capacity by PFC inputs to BLA in adults, but that this capacity is weaker in adolescents. These results provide insight into how the development of PFC inputs may relate to age differences in memory retention and persistence following aversive learning.

25C-NBF, a new psychoactive substance, has addictive and neurotoxic potential in rodents.

The use of new psychoactive substances (NPSs) as a substitute for illegal drugs is increasing rapidly and is a serious threat to public health. 25C-NBF is a newly synthesized phenethylamine-type NPS that acts as a 5-hydroxyindoleacetic acid (5-HT) receptor agonist, but little is known about its pharmacological effects. Considering that NPSs have caused unexpected harmful effects leading to emergency and even death, scientific confirmation of the potential adverse effects of 25C-NBF is essential. In the present study, we investigated whether 25C-NBF has addictive and neurotoxic potential and causes neurochemical changes. In addictive potential assessments, high conditioned place preference (CPP) scores and stable self-administration (SA) were observed in the 25C-NBF groups (CPP [3 mg kg-1]; SA [0.01, 0.03, 0.1 mg kg-1]), suggesting the addictive liability of 25C-NBF. In neurotoxic potential assessments, 25C-NBF treatment (single super-high dose [1 × 15, 30, 40 mg kg-1]; repeated high dose [4 × 8, 15, 30 mg kg-1]) resulted in reduced motor activity (open field test), abnormal motor coordination (rota-rod test) and impaired recognition memory (novel object recognition test), suggesting that 25C-NBF is neurotoxic leading to motor impairment and memory deficits. Subsequently, immunohistochemistry showed that 25C-NBF treatment decreased tyrosine hydroxylase (TH) expression and increased ionized calcium-binding adapter molecule 1 (Iba-1) expression in the striatum. Taken together, our results clearly demonstrate the dangers of recreational use of 25C-NBF, and we suggest that people stop using 25C-NBF and other NPSs whose pharmacological effects are not precisely known.

Side effects of induced lateral eye movements during aversive ideation.

BACKGROUND AND OBJECTIVES: Eye Movement Desensitization and Reprocessing (EMDR) is a treatment for posttraumatic stress disorder. It uses a dual-task approach, in which patients recall an aversive memory while making lateral eye movements. Research has shown that this 'eye movements' intervention reduces subjective memory vividness and emotionality. This study examined whether it also reduces memory accuracy on a visual discrimination task. METHODS: Participants (68 undergraduates) underwent an aversive conditioning phase, in which two pictures of male faces were followed by shock. Then they recalled one face with (experimental condition) and one without (control condition) making lateral eye movements. Finally, they completed a stimulus discrimination test with slightly different faces shortly after the intervention and one day later. RESULTS: Results showed that the eye movements intervention led to increased false-positive rates one day later. LIMITATIONS: Our intervention targeted newly formed memory rather than consolidated memory. CONCLUSIONS: The results inform theory about EMDR's mechanisms of change and suggest that the treatment may have side effects regarding memory accuracy.

It takes two: Bilateral bed nuclei of the stria terminalis mediate the expression of contextual fear, but not of moderate cued fear.

A growing body of research supports a prominent role for the bed nucleus of the stria terminalis (BST) in the expression of adaptive and perhaps even pathological anxiety. The traditional premise that the BST is required for long-duration responses to threats, but not for fear responses to distinct, short-lived cues may, however, be oversimplified. A thorough evaluation of the involvement of the BST in cued and contextual fear is therefore warranted. In a series of preregistered experiments using male Wistar rats, we first addressed the involvement of the BST in cued fear. Following up on earlier work where we found that BST lesions disrupted auditory fear while the animals were in a rather high stress state, we here show that the BST is not required for the expression of more specific fear for the tone under less stressful conditions. In the second part, we corroborate that the same lesion method does attenuate contextual fear. Furthermore, despite prior indications for an asymmetric recruitment of the BST during the expression of anxiety, we found that bilateral lesioning of the BST is required for a significant attenuation of the expression of contextual fear. A functional BST in only one hemisphere resulted in increased variability in the behavioral outcome. We conclude that, in animals that acquired a fear memory with an intact brain, the bilateral BST mediates the expression of contextual fear, but not of unambiguous cued fear.