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1.
Nat Commun ; 13(1): 2403, 2022 May 03.
Artigo em Inglês | MEDLINE | ID: mdl-35504873

RESUMO

C. elegans react to metabolic distress caused by mismatches in oxygen and energy status via distinct behavioral responses. At the molecular level, these responses are coordinated by under-characterized, redox-sensitive processes, thought to initiate in mitochondria. Complex I of the electron transport chain is a major site of reactive oxygen species (ROS) production and is canonically associated with oxidative damage following hypoxic exposure. Here, we use a combination of optogenetics and CRISPR/Cas9-mediated genome editing to exert spatiotemporal control over ROS production. We demonstrate a photo-locomotory remodeling of avoidance behavior by local ROS production due to the reversible oxidation of a single thiol on the complex I subunit NDUF-2.1. Reversible thiol oxidation at this site is necessary and sufficient for the behavioral response to hypoxia, does not respond to ROS produced at more distal sites, and protects against lethal hypoxic exposure. Molecular modeling suggests that oxidation at this thiol residue alters the ability for NDUF-2.1 to coordinate electron transfer to coenzyme Q by destabilizing the Q-binding pocket, causing decreased complex I activity. Overall, site-specific ROS production regulates behavioral responses and these findings provide a mechanistic target to suppress the detrimental effects of hypoxia.


Assuntos
Caenorhabditis elegans , Compostos de Sulfidrila , Animais , Aprendizagem da Esquiva , Caenorhabditis elegans/genética , Caenorhabditis elegans/metabolismo , Complexo I de Transporte de Elétrons/genética , Complexo I de Transporte de Elétrons/metabolismo , Hipóxia , Espécies Reativas de Oxigênio/metabolismo
2.
Commun Biol ; 5(1): 422, 2022 05 05.
Artigo em Inglês | MEDLINE | ID: mdl-35513700

RESUMO

Innate immune surveillance, which monitors the presence of potentially harmful microorganisms and the perturbations of host physiology that occur in response to infections, is critical to distinguish pathogens from beneficial microbes. Here, we show that multidrug resistance-associated protein-1 (MRP-1) functions in the basolateral membrane of intestinal cells to transport byproducts of cellular redox reactions to control both molecular and behavioral immunity in Caenorhabditis elegans. Pseudomonas aeruginosa infection disrupts glutathione homeostasis, leading to the excess production of the MRP-1 substrate, oxidized glutathione (GSSG). Extracellular GSSG triggers pathogen avoidance behavior and primes naïve C. elegans to induce aversive learning behavior via neural NMDA class glutamate receptor-1 (NMR-1). Our results indicate that MRP-1 transports GSSG, which acts as a danger signal capable of warning C. elegans of changes in intestinal homeostasis, thereby initiating a gut neural signal that elicits an appropriate host defense response.


Assuntos
Proteínas de Caenorhabditis elegans , Caenorhabditis elegans , Animais , Aprendizagem da Esquiva , Caenorhabditis elegans/metabolismo , Proteínas de Caenorhabditis elegans/metabolismo , Dissulfeto de Glutationa , Proteínas Associadas à Resistência a Múltiplos Medicamentos/metabolismo , Oxirredução
3.
Eur J Psychotraumatol ; 13(1): 2044661, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35479300

RESUMO

Background: Avoidance describes any action designed to prevent an uncomfortable situation or emotion from occurring. Although it is a common reaction to trauma, avoidance becomes problematic when it is the primary coping strategy, and plays a major role in the development and maintenance of posttraumatic stress disorder (PTSD). Avoidance in PTSD may generalize to non-harmful environmental cues that are perceived to be unsafe. Objective: We tested whether avoidance extends to social cues (i.e. emotional gazes) that are unrelated to trauma. Method: A total of 159 participants (103 who had been exposed to the 2015 Paris terrorist attacks and 56 who had not) performed a gaze-cueing task featuring sad, happy and neutral faces. Attention to the eye area was recorded using an eyetracker. Of the exposed participants, 52 had been diagnosed with PTSD (PTSD+) and 51 had not developed PTSD (PTSD-). As a result of the preprocessing stages, 52 PTSD+ (29 women), 50 PTSD- (20 women) and 53 nonexposed (31 women) participants were included in the final analyses. Results: PTSD+ participants looked at sad eyes for significantly less time than PTSD- and nonexposed individuals. This effect was negatively correlated with the intensity of avoidance symptoms. No difference was found for neutral and happy faces. Conclusions: These findings suggest that maladaptive avoidance in PTSD extends to social processing, in terms of eye contact and others' emotions that are unrelated to trauma. New therapeutic directions could include targeting sociocognitive deficits. Our findings open up new and indirect avenues for overcoming maladaptive avoidance behaviours by remediating eye processing.Trial registration: ClinicalTrials.gov identifier: NCT02810197. HIGHLIGHTS: Avoidance is a key symptom of posttraumatic stress disorder (PTSD).Avoidance is often viewed as limited to reminders linked to the trauma.Results show that attention to the eyes of sad faces is also affected by PTSD. This effect is correlated with avoidance symptoms in PTSD.


Antecedentes: La evitación describe cualquier acción diseñada para prevenir una situación o emoción desagradable. Aunque es una reacción común al trauma, la evitación se vuelve problemática cuando es la principal estrategia de afrontamiento, y desempeña un papel importante en el desarrollo y mantenimiento del trastorno de estrés postraumático (TEPT). La evitación en el TEPT puede generalizarse a señales ambientales no dañinas que se perciben como inseguras. Objetivo: Probamos si la evitación se extiende a las señales sociales (es decir, las miradas emocionales) que no están relacionadas con el trauma. Método: Un total de 159 participantes (103 que habían estado expuestos a los atentados terroristas de París del 2015 y 56 que no lo habían estado) realizaron una tarea de captación de miradas con rostros tristes, felices y neutros. La atención a la zona de los ojos se registró mediante un rastreador ocular. De los participantes expuestos, 52 habían sido diagnosticados con TEPT (TEPT+) y 51 no habían desarrollado TEPT (TEPT-). Resultados: Los participantes con TEPT+ miraron los ojos tristes durante un tiempo significativamente menor que los individuos con TEPT- y los no expuestos. Este efecto se correlacionó negativamente con la intensidad de los síntomas de evitación. No se encontraron diferencias para las caras neutras y felices Conclusiones: Estos hallazgos sugieren que la evitación desadaptativa en el TEPT se extiende al procesamiento social, en cuanto al contacto visual y las emociones de los demás que no están relacionadas con el trauma. Las nuevas direcciones terapéuticas podrían incluir centrarse en los déficits sociocognitivos. Nuestros hallazgos abren vías nuevas e indirectas para superar las conductas de evitación desadaptativas mediante la remediación del procesamiento ocular.


Assuntos
Transtornos de Estresse Pós-Traumáticos , Adaptação Psicológica , Aprendizagem da Esquiva , Sinais (Psicologia) , Emoções , Feminino , Humanos , Masculino , Transtornos de Estresse Pós-Traumáticos/diagnóstico
4.
Physiol Behav ; 251: 113817, 2022 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-35443198

RESUMO

AIMS: Oxidative stress and neuronal death are the primary reasons for the progression of amyloid-beta (Aß) deposition and cognitive deficits in Alzheimer's disease (AD). Ecdysterone (ecdy), a common derivative of ecdysteroids, possesses free radical scavenging and cognitive-improving effects. High-intensity interval training (HIIT) can be a therapeutic strategy for improving cognitive decline and oxidative stress. The present study was aimed to evaluate the effect of HIIT exercise and ecdy consumption synergistically on the changes in learning and memory functions, activities of hippocampal antioxidant enzymes, and neuronal population after AD induced by Aß in male rats. MATERIALS AND METHODS: Following ten days of Aß injection, HIIT exercise and ecdy treatment (10 mg/kg/day; P.O.) were initiated and continued for eight consecutive weeks in rats. At the end of the treatment period, the rat's learning and memory functions were assessed using Morris water maze and passive avoidance tests. The activity of superoxide dismutase (SOD), catalase (CAT), glutathione reductase (GRx), and changes in neuronal population were evaluated in rats' brains. RESULTS: The results indicated that Aß injection disrupted spatial/passive avoidance learning and memory in both tests, accompanied by a decrease in the SOD and CAT (as endogenous antioxidants) in rats' hippocampus. Additionally, Aß injection resulted in neuronal loss in the cerebral cortex and hippocampus. Although the consumption of ecdy separately improved spatial/passive avoidance learning and memory impairments, recovered hippocampal activity of SOD, CAT, GRx, and prevented the hippocampal neuronal loss, its combination along with HIIT resulted in a more powerful and effective amelioration in all the above-mentioned Aß-neuropathological changes. CONCLUSION: Our results confirm that a combination of HIIT and ecdy treatment could be a promising potential therapeutic option against AD-associated cognitive decline, owing to their free radical scavenging and neuroprotective properties.


Assuntos
Doença de Alzheimer , Treinamento Intervalado de Alta Intensidade , Doença de Alzheimer/tratamento farmacológico , Doença de Alzheimer/terapia , Peptídeos beta-Amiloides/metabolismo , Animais , Antioxidantes/farmacologia , Antioxidantes/uso terapêutico , Aprendizagem da Esquiva , Modelos Animais de Doenças , Ecdisterona/farmacologia , Ecdisterona/uso terapêutico , Radicais Livres/efeitos adversos , Hipocampo/metabolismo , Masculino , Aprendizagem em Labirinto , Fragmentos de Peptídeos/farmacologia , Ratos , Superóxido Dismutase/metabolismo
5.
Psicothema ; 34(2): 240-248, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-35485537

RESUMO

BACKGROUND: Evidence about how cognitive fusion (CF) and experiential avoidance (EA) interact with emotional distress underlines the importance of analyzing the interrelationships between the different processes of psychological inflexibility in order to improve ways of addressing emotional problems. This study analyzes the moderating effect of CF, EA and activation (A) in relation to four criteria of anxiety and depression. METHOD: A cross-sectional study of a clinical sample of adults was carried out by means of a questionnaire administered before (N = 172) and 6 months after (N = 114) participation in a clinical study. RESULTS: Regression analyses gave results which were consistent in the two evaluations. The EAxCF interaction modulated anxiety symptomatology, whereas A was not a significant predictor. Nevertheless, a reduction in A was the principal modulating condition in the symptomatology of depression; and although CF and EA did act as independent predictors, the EAxCF interaction was not significant. CONCLUSIONS: The presence and intensity of manifestations of emotional distress are explained and modulated by the progressive concurrence of CF, EA and reduction in A. The use of therapeutic approaches which increase activation could be a beneficial strategy with regard to decreasing cognitive fusion and experiential avoidance.


Assuntos
Aprendizagem da Esquiva , Depressão , Adulto , Ansiedade/psicologia , Aprendizagem da Esquiva/fisiologia , Cognição , Estudos Transversais , Depressão/psicologia , Humanos
6.
Sci Rep ; 12(1): 6576, 2022 Apr 21.
Artigo em Inglês | MEDLINE | ID: mdl-35449167

RESUMO

Conflicts between avoiding feared stimuli versus approaching them for competing rewards are essential for functional behavior and anxious psychopathology. Yet, little is known about the underlying decision process. We examined approach-avoidance decisions and their temporal dynamics when avoiding Pavlovian fear stimuli conflicted with gaining rewards. First, a formerly neutral stimulus (CS+) was repeatedly paired with an aversive stimulus (US) to establish Pavlovian fear. Another stimulus (CS-) was never paired with the US. A control group received neutral tones instead of aversive USs. Next, in each of 324 trials, participants chose between a CS-/low reward and a CS+/high reward option. For the latter, probability of CS+ presentation (Pavlovian fear information) and reward magnitude (reward information) varied. Computer mouse movements were tracked to capture the decision dynamics. Although no more USs occurred, pronounced and persistent costly avoidance of the Pavlovian fear CS+ was found. Time-continuous multiple regression of movement trajectories revealed a stronger and faster impact of Pavlovian fear compared to reward information during decision-making. The impact of fear information, but not reward information, modestly decreased across trials. These findings suggest a persistently stronger weighting of fear compared to reward information during approach-avoidance decisions, which may facilitate the development of pathological avoidance.


Assuntos
Aprendizagem da Esquiva , Medo , Ansiedade , Humanos , Movimento , Recompensa
7.
Sci Rep ; 12(1): 6441, 2022 Apr 19.
Artigo em Inglês | MEDLINE | ID: mdl-35440704

RESUMO

Wind energy production has expanded as an alternative to carbon emitting fossil fuels, but is causing impacts on wildlife that need to be addressed. Soaring birds show concerning rates of collision with turbine rotor blades and losses of critical habitat. However, how these birds interact with wind turbines is poorly understood. We analyzed high-frequency GPS tracking data of 126 black kites (Milvus migrans) moving near wind turbines to identify behavioural mechanisms of turbine avoidance and their interaction with environmental variables. Birds flying within 1000 m from turbines and below the height of rotor blades were less likely to be oriented towards turbines than expected by chance, this pattern being more striking at distances less than 750 m. Within the range of 750 m, birds showed stronger avoidance when pushed by the wind in the direction of the turbines. Birds flying above the turbines did not change flight directions with turbine proximity. Sex and age of birds, uplift conditions and turbine height, showed no effect on flight directions although these factors have been pointed as important drivers of turbine collision by soaring birds. Our findings suggest that migrating black kites recognize the presence of wind turbines and behave in a way to avoid then. This may explain why this species presents lower collision rates with wind turbines than other soaring birds. Future studies should clarify if turbine avoidance behaviour is common to other soaring birds, particularly those that are facing high fatality rates due to collision.


Assuntos
Aprendizagem da Esquiva , Aves , Animais , Animais Selvagens , Ecossistema
8.
Eur J Pharmacol ; 923: 174928, 2022 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-35398030

RESUMO

Agmatine is a polyamine suggested to act as a supposed neurotransmitter in the brain. Evidence has indicated that acute agmatine administration might modulate memory. The present study aimed to investigate the effect of repeated agmatine treatment on passive avoidance memory, hippocampal calcium-calmodulin-dependent protein kinase II-alpha (CaMKII-α), and Extracellular Signal-Regulated Kinase (ERK) signaling pathways in naive mice. Adult male NMRI mice were treated with agmatine (10, 20, 30, 40, and 80 mg/kg/ip) or saline for 11 days. Acquisition and retention tests of passive avoidance memory were performed on days 10 and 11, respectively. Following the memory retention test, the hippocampi were assessed for the levels of CaMKII-α and ERK using the western blotting technique. The results revealed the dose-dependent effect of agmatine on the passive avoidance memory. Accordingly, the memory was impaired in lower doses, but was improved in higher ones. Agmatine in none of the doses affected the nociception of the mice in tail-flick test. Furthermore, agmatine increased the phosphorylation of CaMKII-α and ERK in the hippocampus at memory enhancing doses, while ERK phosphorylation decreased following the impairing doses of agmatine. Thus, the dose-dependent effect of agmatine on memory might be related to its modulatory effect on CaMKII-α and ERK signal transduction, eventually regulating the memory process.


Assuntos
Agmatina , Proteína Quinase Tipo 2 Dependente de Cálcio-Calmodulina , Agmatina/metabolismo , Agmatina/farmacologia , Animais , Aprendizagem da Esquiva , Proteína Quinase Tipo 2 Dependente de Cálcio-Calmodulina/metabolismo , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Hipocampo , Masculino , Camundongos , Fosforilação , Transdução de Sinais
9.
Behav Ther ; 53(3): 414-427, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-35473646

RESUMO

Avoidance is one of the purported benefits and harms of trigger warnings-alerts that upcoming content may contain traumatic themes. Yet, previous research has focused primarily on emotional responses. Here, we used a trauma analogue design to assess people's avoidance behavior in response to stimuli directly related to an analogue trauma event. University undergraduates (n = 199) watched a traumatic film and then viewed film image stills preceded by either a trigger warning or a neutral task instruction. Participants had the option to "cover" and avoid each image. Apart from a minor increase in avoidance when a warning appeared in the first few trials, we found that participants did not overall avoid negative stimuli prefaced with a trigger warning any more than stimuli without a warning. In fact, participants were reluctant overall to avoid distressing images; only 12.56% (n = 25) of participants used the option to cover such images when given the opportunity to do so. Furthermore, we did not find any indication that trigger warning messages help people to pause and emotionally prepare themselves to view negative content. Our results contribute to the growing body of literature demonstrating that warnings seem trivially effective in achieving their purported goals.


Assuntos
Aprendizagem da Esquiva , Emoções , Humanos , Estudantes
10.
Learn Mem ; 29(5): 120-125, 2022 05.
Artigo em Inglês | MEDLINE | ID: mdl-35428728

RESUMO

We observed differences in cognitive functions between middle-aged female and male Wistar rats. Both (like youngsters) discriminated new versus familiar objects, showing similar short- and long-term memory (STM and LTM, respectively). Only females show robust LTM for new location of an object. Both successfully form LTM of inhibitory avoidance, though males appeared to be amnesic for memory persistence. Habituation, locomotion, horizontal exploration, "stereotypies," fear, and anxiety-like behavior were similar for both, while vertical exploration was significantly higher in middle-aged and younger females. Therefore, sex-dependent differences in some cognitive functions and behaviors must be considered when designing and interpreting learning and memory studies.


Assuntos
Aprendizagem , Memória de Longo Prazo , Animais , Ansiedade , Aprendizagem da Esquiva , Medo , Feminino , Masculino , Memória de Curto Prazo , Ratos , Ratos Wistar
11.
eNeuro ; 9(2)2022.
Artigo em Inglês | MEDLINE | ID: mdl-35396256

RESUMO

θ-Scale coordination of prelimbic medial prefrontal cortex (mPFC) local field potentials (LFPs) and its influence via direct or indirect projections to the ventral hippocampus (vHC) and dorsal hippocampus (dHC) during spatial learning remains poorly understood. We hypothesized that θ frequency coordination dynamics within and between the mPFC, dHC, and vHC would be predetermined by the level of connectivity rather than reflecting differing circuit throughput relationships depending on cognitive demands. Moreover, we hypothesized that coherence levels would not change during learning of a complex spatial avoidance task. Adult male rats were bilaterally implanted with EEG electrodes and LFPs recorded in each structure. Contrary to predictions, θ coherence averaged across "Early" or "Late" training sessions in the mPFC-HC, mPFC-mPFC, and HC-HC increased as a function of task learning. Coherence levels were also highest between the indirectly connected mPFC-dHC circuit, particularly during early training. Although mPFC postacquisition coherence remained higher with dHC than vHC, dynamic mPFC coherence patterns with both hippocampal poles across avoidance epochs were similar. In the 3 s before avoidance, a regional temporal sequence of transitory coherence peaks emerged between the mPFC-mPFC, the mPFC-HC, and then dHC-dHC. During this sequence, coherence within θ bandwidth fluctuated between epochs at distinct subfrequencies, suggesting frequency-specific roles for the propagation of task-relevant processing. On a second timescale, coherence frequency within and between the mPFC and hippocampal septotemporal axis change as a function of avoidance learning and cognitive demand. The results support a role for θ coherence subbandwidths, and specifically an 8- to 9-Hz mPFC θ signal, for generating and processing qualitatively different types of information in the organization of spatial avoidance behavior in the mPFC-HC circuit.


Assuntos
Córtex Pré-Frontal , Ritmo Teta , Animais , Aprendizagem da Esquiva , Eletroencefalografia , Hipocampo , Masculino , Ratos
12.
Behav Brain Res ; 427: 113868, 2022 Jun 03.
Artigo em Inglês | MEDLINE | ID: mdl-35364111

RESUMO

Associative learning and memory mechanisms drive interoceptive signaling along the gut-brain axis, thus shaping affective-emotional reactions and behavior. Specifically, learning to predict potentially harmful, visceral pain is assumed to succeed within very few trials. However, the temporal dynamics of cerebellar and cerebral fMRI signal changes underlying early acquisition and extinction of learned fear signals and the concomitant evolvement of safety learning remain incompletely understood. 3 T fMRI data of healthy individuals from three studies were uniformly processed across the whole brain and the cerebellum. All studies employed differential delay conditioning (N = 94) with one visual cue (CS+) being repeatedly paired with visceral pain as unconditioned stimulus (US) while a second cue remained unpaired (CS-). During subsequent extinction (N = 51), all CS were presented without US. Behavioral results revealed increased CS+-aversiveness and CS--pleasantness after conditioning and diminished valence ratings for both CS following extinction. During early acquisition, the CS- induced linearly increasing neural activation in the insula, midcingulate cortex, hippocampus, precuneus as well as cerebral and cerebellar somatomotor regions. The comparison between acquisition and extinction phases yielded a CS--induced linear increase in the posterior cingulate cortex and precuneus during early acquisition, while there was no evidence for linear fMRI signal changes for the CS+ during acquisition and for both CS during extinction. Based on theoretical accounts of discrimination and temporal difference learning, these results suggest a gradual evolvement of learned safety cues that engage emotional arousal, memory, and cortical modulatory networks. As safety signals are presumably more difficult to learn and to discriminate from learned threat cues, the underlying temporal dynamics may reflect enhanced salience and prediction processing as well as increasing demands for attentional resources and the integration of multisensory information. Maladaptive responses to learned safety signals are a clinically relevant phenotype in multiple conditions, including chronic visceral pain, and can be exceptionally resistant to modification or extinction. Through sustained hypervigilance, safety seeking constitutes one key component in pain and stress-related avoidance behavior, calling for future studies targeting the mechanisms of safety learning and extinction to advance current cognitive-behavioral treatment approaches.


Assuntos
Imageamento por Ressonância Magnética , Dor Visceral , Aprendizagem da Esquiva , Mapeamento Encefálico/métodos , Extinção Psicológica/fisiologia , Medo/fisiologia , Humanos , Transtornos Fóbicos
14.
Eur J Neurosci ; 55(6): 1532-1546, 2022 03.
Artigo em Inglês | MEDLINE | ID: mdl-35266590

RESUMO

Storage of aversive memories is of utmost importance for survival, allowing animals to avoid upcoming similar stimuli. However, without reinforcement, the learned avoidance response gradually decreases over time. Although the molecular mechanisms controlling this extinction process are not well known, there is evidence that the endocannabinoid system plays a key role through CB1 receptor-mediated modulation of cholinergic signaling. In this study, we measured fear extinction throughout 7 months using naïve rats, assessed in passive avoidance (PA) test in a non-reinforced manner. Then, we evaluated the effect of gentle handling and non-aversive novel object recognition test (NORT) on the extinction and expression of fear memories by measuring passive avoidance responses. Neurochemical correlates were analyzed by functional autoradiography for cannabinoid, cholinergic, and dopaminergic receptors. Despite results showing a gradual decrease of passive avoidance response, it did not fully disappear even after 7 months, indicating the robustness of this process. Meanwhile, in rats that received gentle handling or performed NORT after receiving the PA aversive stimulus, extinction occurred within a week. In contrast, gentle handling performed before receiving the aversive stimulus exacerbated fear expression and triggered escape response in PA. The neurochemical analysis showed increased cannabinoid and cholinergic activity in the nucleus basalis magnocellularis (NBM) in rats that had performed only PA, as opposed to rats that received gentle handling before PA. Additionally, a correlation between CB1 mediated-signaling in the NBM and freezing in PA was found, suggesting that the endocannabinoid system might be responsible for modulating fear response induced by aversive memories.


Assuntos
Núcleo Basal de Meynert , Canabinoides , Animais , Aprendizagem da Esquiva/fisiologia , Núcleo Basal de Meynert/metabolismo , Colinérgicos/farmacologia , Endocanabinoides/metabolismo , Extinção Psicológica , Medo/fisiologia , Ratos , Receptor CB1 de Canabinoide/metabolismo
15.
Neurosci Lett ; 778: 136585, 2022 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-35318075

RESUMO

Ethanol-induced conditioned taste aversion (CTA) is greater in late adolescence or young adulthood than in early adolescence. The role of the sigma receptor system in this age-related difference has not been extensively explored, particularly in female rats. This study assessed the effects of the activation of sigma-1 receptors (S1-R), via the selective S1-R agonist PRE-084, on ethanol-induced CTA at early or at terminal adolescence/emerging adulthood (28 or 56 days-old at the beginning of the procedures, respectively) in female Wistar rats. The modulation of binge-like ethanol intake by PRE-084 was assessed at terminal adolescence. S1-R activation at the acquisition of ethanol-induced CTA attenuated such learning at terminal but not at early adolescence. PRE-084 did not significantly affect ethanol binge drinking in the terminal adolescents. These results highlight the role of S1-R in ethanol-induced CTA and suggest that differential functionality of this transmitter system may underlie age-specific sensitivities to the aversive effects of ethanol.


Assuntos
Etanol , Paladar , Consumo de Bebidas Alcoólicas , Animais , Aprendizagem da Esquiva , Etanol/farmacologia , Feminino , Morfolinas , Ratos , Ratos Wistar , Receptores sigma
16.
Proc Natl Acad Sci U S A ; 119(11): e2115533119, 2022 03 15.
Artigo em Inglês | MEDLINE | ID: mdl-35254908

RESUMO

SignificancePhysiological stress triggers avoidance behavior, allowing the animals to stay away from potential threats and optimize their chance of survival. Mitochondrial disruption, a common physiological stress in diverse species, induces the nematode Caenorhabditis elegans to avoid non-pathogenic bacteria through a serotonergic neuronal circuit. We find that distinct neurons, communicated through serotonin and a specific serotonin receptor, are required for the formation and retrieval of this learned aversive behavior. This learned avoidance behavior is associated with increased serotonin synthesis, altered neuronal response property, and reprogramming of locomotion patterns. The circuit and neuromodulatory mechanisms described here offer important insights for stress-induced avoidance behavior.


Assuntos
Caenorhabditis elegans/fisiologia , Mitocôndrias/metabolismo , Receptores de Serotonina/metabolismo , Neurônios Serotoninérgicos/fisiologia , Serotonina/metabolismo , Estresse Fisiológico , Animais , Aprendizagem da Esquiva , Interações Hospedeiro-Patógeno , Interneurônios/metabolismo , Aprendizagem
17.
Biochem Biophys Res Commun ; 602: 57-62, 2022 04 30.
Artigo em Inglês | MEDLINE | ID: mdl-35255434

RESUMO

Ghrelin is an orexigenic gastric hormone that promotes feeding behaviors and regulating energy homeostasis in both humans and rodents. Our previous studies have shown that ghrelin, when locally infused into the basolateral amygdala (BLA), blocks both acquisition and extinction of conditioned taste aversion (CTA) memory in rats. In this study, we further investigated the effect of virus-mediated overexpression of ghrelin receptor growth hormone secretagogue receptor 1a (GHS-R1a) in BLA pyramidal neurons on CTA memory processes. We found that upregulation of GHS-R1a expression in BLA pyramidal neurons repressed CTA extinction while it had no effect on CTA acquisition. In addition, we reported that local infusion of the endogenous GHS-R1a antagonist, liver-expressed antimicrobial peptide 2 (LEAP2), in the BLA abolished the inhibitory effect of increased GHS-R1a on CTA memory extinction. Those findings provide new supportive evidence that ghrelin/GHS-R1a signaling in the BLA circuit shapes emotional memory processes.


Assuntos
Aprendizagem da Esquiva , Complexo Nuclear Basolateral da Amígdala , Receptores de Grelina , Animais , Complexo Nuclear Basolateral da Amígdala/metabolismo , Comportamento Alimentar , Grelina/farmacologia , Ratos , Receptores de Grelina/metabolismo , Paladar/fisiologia
18.
Behav Res Ther ; 151: 104056, 2022 04.
Artigo em Inglês | MEDLINE | ID: mdl-35231778

RESUMO

Avoiding stimuli that were previously associated with threat is essential for adaptive functioning, but excessive avoidance that persists in the absence of threat can turn dysfunctional and results in severe impairments. Fear and avoidance conditioning models have substantially contributed to the understanding of safety behaviors towards learnt fear stimuli. Safety behaviors are executed in the presence of a feared stimulus to prevent the upcoming threat and are well-established in laboratory models. Avoidance of learnt fear, i.e., avoidance of the feared stimulus itself, is typically initiated before the onset of a feared stimulus: individuals oftentimes avoid fear stimuli to prevent negative emotions evoked by them or ultimately the associated threat. Avoidance of learnt fear is surprisingly understudied despite its prevalence in pathological anxiety. The current overview proposes potential behavioral mechanisms and neural circuits of avoidance of learnt fear in humans, and discusses findings and paradigms suitable for examining it. Specifically, higher-order conditioning, decision making paradigms, and context-cue conditioning investigate distinct forms of avoidance of learnt fear. We also discuss the clinical prospects and future directions of research in avoidance of learnt fear.


Assuntos
Condicionamento Clássico , Extinção Psicológica , Aprendizagem da Esquiva/fisiologia , Condicionamento Clássico/fisiologia , Condicionamento Operante , Extinção Psicológica/fisiologia , Medo/psicologia , Humanos
19.
Child Adolesc Ment Health ; 27(2): 199-200, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-35289067

RESUMO

The characteristic features of personality disorder that are found in older people are also present in young people. These features are currently not diagnosed as personality problems by most UK practitioners, through a mixture of fear and prejudice, which is used to justify this avoidant diagnostic behaviour. A simple solution is offered. State that personality function is 'disordered' in those who cross the threshold for diagnosis but emphasise that it is often ephemeral and can be managed.


Assuntos
Medo , Transtornos da Personalidade , Adolescente , Idoso , Aprendizagem da Esquiva , Humanos , Transtornos da Personalidade/diagnóstico , Transtornos da Personalidade/terapia , Preconceito
20.
Rev Bras Parasitol Vet ; 31(1): e014021, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35293429

RESUMO

This study aimed to evaluate foraging distance (FD) from the dung, parasitological and physiological factors in 18 Crioula Lanada lambs naturally infected by nematodes with three infection levels (IL) in a Voisin Grazing System. In the pre-experimental phase animal feces collection, deworming, observer training, animal adaptation and dung demarcation were carried out; in the experimental phase, grazing distance, feces, pasture and blood sampling. An initial exploratory analysis was carried out (Kruskal-Wallis test). Fixed predictors were selected with a cumulative logit regression model; an ordinal logistic regression mixed model identified influencing factors of ordinal responses for (i) FD, (ii) infective larvae quantity (L3). Animals approached the dung when the radiation or temperature were more intense (P < 0.05). Paddock entry/exit, IgG and L3 influenced FD over time (P < 0.05). L3, in turn, was influenced by IL, FEC and corpuscular volume (CV). In the High IL group, FD varied between 60-100 cm. Greater L3 and FEC were found in the High and Low IL from the 4th week (P < 0.05). Naturally infected Crioula Lanada lambs increased the distance from the dung, which was not related to IL but to the dynamics of solar radiation and parasitological and immunological factors.


Assuntos
Nematoides , Doenças dos Ovinos , Animais , Aprendizagem da Esquiva , Fezes/parasitologia , Larva , Ovinos , Doenças dos Ovinos/parasitologia
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