RESUMEN
Human literature has linked adverse early life experiences with an increased risk to develop violent behaviors in both boys and girls. We have previously shown that male rats submitted to stress during the peripuberty period display as adults abnormal aggressive behavior against both male intruders and female partners. In the present study, we examined whether the same stress protocol would affect the development of aggressive behaviors in female rats. We evaluated the behavior of these peripuberty stressed female rats when confronted, at adulthood, with either female or male intruders, and during their cohabitation with male partners. Given that estrus cycle influences mood and aggressive behaviors, female aggressive behavior was assessed at different estrus cycle phases: estrus and diestrus, and during pregnancy and lactancy. Additionally, we evaluated postpartum plasma levels of vasopressin, oxytocin and corticosterone, hormones associated with aggression and the regulation of social behavior. Compared to control females, females submitted to stressful events during puberty exhibited higher and more sustained rates of aggression during adulthood independently on the estrus cycle or the sex of the intruder, and they had higher levels of plasma vasopressin. Significant correlations between plasma levels of vasopressin and corticosterone and aggressive behavior were also found. Strikingly, our results showed opposite intragroup correlations suggesting a different role of these hormones on aggression depending on life experiences. We provide here an animal model, devoid of cultural influences strongly supporting a role for biological factors in the development of aggressive behaviors following exposure to stressful events at puberty in females.
Asunto(s)
Agresión/psicología , Envejecimiento/psicología , Maduración Sexual , Estrés Psicológico/psicología , Envejecimiento/metabolismo , Animales , Corticosterona/sangre , Ciclo Estral/metabolismo , Femenino , Lactancia/metabolismo , Lactancia/psicología , Oxitocina/sangre , Embarazo , Ratas , Estrés Psicológico/sangre , Vasopresinas/sangreRESUMEN
Emerging evidence indicates that certain behavioral traits, such as anxiety, are associated with the development of depression-like behaviors after exposure to chronic stress. However, single traits do not explain the wide variability in vulnerability to stress observed in outbred populations. We hypothesized that a combination of behavioral traits might provide a better characterization of an individual's vulnerability to prolonged stress. Here, we sought to determine whether the characterization of relevant behavioral traits in rats could aid in identifying individuals with different vulnerabilities to developing stress-induced depression-like behavioral alterations. We also investigated whether behavioral traits would be related to the development of alterations in the hypothalamic-pituitary-adrenal axis and in brain activity - as measured through phosphorylation of extracellular signal-regulated kinase 1/2 (ERK1/2)--in response to an acute stressor following either sub-chronic (2 weeks) or chronic (4 weeks) unpredictable stress (CUS). Sprague-Dawley rats were characterized using a battery of behavioral tasks, and three principal traits were identified: anxiety, exploration and activity. When combined, the first two traits were found to explain the variability in the stress responses. Our findings confirm the increased risk of animals with high anxiety developing certain depression-like behaviors (e.g., increased floating time in the forced swim test) when progressively exposed to stress. In contrast, the behavioral profile based on combined low anxiety and low exploration was resistant to alterations related to social behaviors, while the high anxiety and low exploration profile displayed a particularly vulnerable pattern of physiological and neurobiological responses after sub-chronic stress exposure. Our findings indicate important differences in animals' vulnerability and/or resilience to the effects of repeated stress, particularly during initial or intermediate levels of stress exposure, and they highlight that the behavioral inhibition profile of an animal provides a particular susceptibility to responding in a deleterious manner to stress.
Asunto(s)
Adaptación Psicológica/fisiología , Conducta Animal/fisiología , Encéfalo/metabolismo , Depresión/fisiopatología , Sistema Hipotálamo-Hipofisario/fisiopatología , Sistema Hipófiso-Suprarrenal/fisiopatología , Estrés Psicológico/complicaciones , Animales , Encéfalo/fisiopatología , Depresión/psicología , Sistema Hipotálamo-Hipofisario/metabolismo , Sistema de Señalización de MAP Quinasas/fisiología , Masculino , Proteína Quinasa 1 Activada por Mitógenos/metabolismo , Proteína Quinasa 3 Activada por Mitógenos/metabolismo , Personalidad/fisiología , Fosforilación , Sistema Hipófiso-Suprarrenal/metabolismo , Ratas , Ratas Sprague-Dawley , Resiliencia Psicológica , Estrés Psicológico/fisiopatologíaRESUMEN
Exposure to stress can affect the establishment of dominance hierarchies. In our model, a social hierarchy established by two male rats during a first encounter is not maintained 1 week later. If one of the two rats is stressed, the stressed rat becomes subordinate and the hierarchy that is formed is maintained. In this study, we investigated the changes in the expression of oxytocin (Otr) and vasopressin (V1aR) receptor genes in the medial amygdala (MeA) and the lateral septum (LS) in the hours following hierarchy establishment under both stressed and basal conditions. We found that the potentiation of a social hierarchy induced by stress is accompanied by social status- and region-specific changes in the expression of Otr mRNA in the MeA 3 h after the social encounter. At this time point, no evidence was found for the regulation of V1aR mRNA in any of the brain regions examined. Results from pharmacological experiments involving the microinfusion of a specific OTR antagonist immediately after the acquisition of a subordinate status under basal, non-stress conditions suggested a role for this receptor in the MeA on the long-term establishment of the subordinate status. Altogether, these findings highlight a role for the oxytocinergic system in the mechanisms through which stress facilitates the long-term establishment of a social hierarchy.
Asunto(s)
Amígdala del Cerebelo/fisiología , Receptores de Oxitocina/fisiología , Predominio Social , Animales , Masculino , Ratas , Ratas Wistar , Factores de TiempoRESUMEN
Although the relationship between stress intensity and memory function is generally believed to follow an inverted-U-shaped curve, strikingly this phenomenon has not been demonstrated under the same experimental conditions. We investigated this phenomenon for rats' performance in a hippocampus-dependent learning task, the radial arm water maze (RAWM). Variations in stress intensity were induced using different water temperatures (25°C, 19°C, and 16°C), which elicited increased plasma corticosterone levels. During spatial training over three consecutive days, an inverted-U shape was found, with animals trained at 19°C making fewer errors than animals trained at either higher (16°C) or lower (25°C) stress conditions. Interestingly, this function was already observed by the last trial of day 1 and maintained on the first day trial of day 2. A long-term recall probe test administered under equal temperature conditions (20°C) revealed differences in performance according to the animals' former training conditions; i.e., platform searching for rats trained at 25°C was less accurate than for rats trained at either 16°C or 19°C. In reversal learning, groups trained at both 19°C and 25°C showed better performance than the 16°C group. We also found an interaction between anxiety and exploration traits on how individuals were affected by stressors during spatial learning. In summary, our findings confirm, for the first time, the existence of an inverted-U-shape memory function according to stressor intensity during the early learning and memory phases in a hippocampus-dependent task, and indicate the existence of individual differences related to personality-like profiles for performance at either high or low stress conditions.
Asunto(s)
Aprendizaje/fisiología , Percepción Espacial/fisiología , Estrés Psicológico/fisiopatología , Análisis de Varianza , Animales , Corticosterona/sangre , Conducta Exploratoria/fisiología , Individualidad , Masculino , Aprendizaje por Laberinto/fisiología , Recuerdo Mental/fisiología , Motivación/fisiología , Análisis de Componente Principal , Ratas , Ratas Wistar , Retención en Psicología/fisiología , Estrés Psicológico/sangre , Natación/psicología , TemperaturaRESUMEN
The basolateral nucleus of the amygdala (BLA) plays a key role in emotional arousal and anxiety, and expresses high levels of corticotropin-releasing factor receptor (CRFR)1. In rat brain slices, we have recently shown that afferent activation of the BLA is increased following application of exogenous corticotropin-releasing factor (CRF). Here we examined the impact of chronic unpredictable stress (CUS) on this effect of CRF and whether blockade of CRFR1 could prevent stress-induced changes in the electrophysiological response, the animal's behavior and in cell proliferation in the hippocampus. The behavior of the rats was monitored via a series of tests that formed part of the CUS. Electrophysiological measures of the BLA response to CRF, cell proliferation in the dentate gyrus and the expression of CRF and CRFR1 mRNA in amygdaloid nuclei were determined ex vivo after completion of the CUS. CRF-induced potentiation of afferent activation of the BLA was reduced in rats exposed to CUS, an effect that was inhibited by chronic antagonism of CRFR1. Furthermore, the reduction in BLA response to CRF was correlated with the anxiety trait of the animals, determined prior to initiation of the CUS. These results implicate CRFR1 in chronic stress-induced alterations in amygdala function and behavior. Furthermore, they show that CRFR1 antagonists can prevent changes induced by chronic stress, in particular in those animals that are highly anxious.
Asunto(s)
Amígdala del Cerebelo/metabolismo , Trastornos de Ansiedad/metabolismo , Hormona Liberadora de Corticotropina/metabolismo , Predisposición Genética a la Enfermedad/genética , Receptores de Hormona Liberadora de Corticotropina/metabolismo , Estrés Psicológico/metabolismo , Potenciales de Acción/efectos de los fármacos , Potenciales de Acción/genética , Animales , Trastornos de Ansiedad/tratamiento farmacológico , Trastornos de Ansiedad/genética , Conducta Animal/efectos de los fármacos , Conducta Animal/fisiología , Biomarcadores/análisis , Biomarcadores/metabolismo , Proliferación Celular , Enfermedad Crónica , Hormona Liberadora de Corticotropina/genética , Hipocampo/citología , Hipocampo/fisiología , Antígeno Ki-67/análisis , Antígeno Ki-67/metabolismo , Masculino , Plasticidad Neuronal/efectos de los fármacos , Plasticidad Neuronal/genética , Técnicas de Cultivo de Órganos , Pirimidinas/farmacología , Carácter Cuantitativo Heredable , ARN Mensajero/efectos de los fármacos , ARN Mensajero/metabolismo , Ratas , Receptores de Hormona Liberadora de Corticotropina/antagonistas & inhibidores , Receptores de Hormona Liberadora de Corticotropina/genética , Estrés Psicológico/tratamiento farmacológico , Estrés Psicológico/genéticaRESUMEN
The polysialylated neural cell adhesion molecule (PSA-NCAM) has been implicated in activity-dependent synaptic remodeling and memory formation. Here, we questioned whether training-induced modulation of PSA-NCAM expression might be related to individual differences in spatial learning abilities. At 12 h posttraining, immunohistochemical analyses revealed a learning-induced up-regulation of PSA-NCAM in the hippocampal dentate gyrus that was related to the spatial learning abilities displayed by rats during training. Specifically, a positive correlation was found between latency to find the platform and subsequent activated PSA levels, indicating that greater induction of polysialylation was observed in rats with the slower acquisition curve. At posttraining times when no learning-associated activation of PSA was observed, no such correlation was found. Further experiments revealed that performance in the massed water maze training is related to a pattern of spatial learning and memory abilities, and to learning-related glucocorticoid responsiveness. Taken together, our findings suggest that the learning-related neural circuits of fast learners are better suited to solving the water maze task than those of slow learners, the latter relying more on structural reorganization to form memory, rather than the relatively economic mechanism of altering synaptic efficacy that is likely used by the former.
Asunto(s)
Corticosterona/sangre , Giro Dentado/metabolismo , Aprendizaje por Laberinto/fisiología , Molécula L1 de Adhesión de Célula Nerviosa/metabolismo , Neuronas/metabolismo , Ácidos Siálicos/metabolismo , Análisis de Varianza , Animales , Giro Dentado/citología , Inmunohistoquímica , Individualidad , Masculino , Memoria , Fibras Musgosas del Hipocampo/metabolismo , Plasticidad Neuronal/fisiología , Ratas , Ratas Wistar , Tiempo de Reacción/fisiología , Percepción Espacial/fisiología , Sinapsis/metabolismo , Factores de Tiempo , Regulación hacia ArribaRESUMEN
Previous studies showed that exposure of rats to chronic restraint stress for 21 days enhances subsequent contextual fear conditioning. Since recent evidence suggest that this effect is not dependent on stress-induced neurodegenerative processes, but to elevated training-elicited glucocorticoid release in chronically stressed animals, we aimed to explore here whether a single exposure to restraint stress, which is not expected to induce neuronal damage, would also affect contextual fear conditioning. We also questioned whether post-training corticosterone levels might be associated with any potential effect of stress on fear conditioning. Adult male Wistar rats were exposed to acute restraint stress for 2 h and, two days later, trained in the contextual fear conditioning task, under training conditions involving either moderate (0.4 mA shock) or high (1 mA shock) stress levels. The results showed that acute stress enhanced conditioned freezing at both training conditions, although data from the 1 mA shock intensity experiment only approached significance. Stressed animals were shown to display higher post-training corticosterone levels. Furthermore, the facilitating effect of prior stress was not evident when animals were trained in the hippocampal-independent auditory-cued conditioning task. Therefore, these findings support the idea that stress experiences preceding exposure to new types of stressors facilitate the development of contextual fear conditioning. They also indicate that not only repeated, but also a single exposure to aversive stimulation is sufficient to facilitate context-dependent fear conditioning, and suggest that increased glucocorticoid release at training might be implicated in the mechanisms mediating the memory facilitating effects induced by prior stress experiences.
Asunto(s)
Reacción de Prevención/fisiología , Condicionamiento Psicológico/fisiología , Corticosterona/fisiología , Miedo/fisiología , Estrés Fisiológico/fisiopatología , Estimulación Acústica , Animales , Aprendizaje por Asociación/fisiología , Miedo/psicología , Sistema Hipotálamo-Hipofisario/fisiología , Masculino , Sistema Hipófiso-Suprarrenal/fisiología , Práctica Psicológica , Ratas , Ratas Wistar , Estrés Fisiológico/psicologíaRESUMEN
BACKGROUND: Cell adhesion molecule function is involved in hippocampal synaptic plasticity and associated with memory consolidation. At the infragranular zone of the dentate gyrus, neurons expressing the polysialylated form of the neural cell adhesion molecule (NCAM PSA) transiently increase their frequency 12 hours after training in different tasks. METHODS: Using immunohistochemical procedures, we investigated NCAM polysialylation following training in a contextual fear conditioning paradigm that employed increasing shock intensities to separately model stressful and traumatic experiences in adult male Wistar rats. RESULTS: Fear conditioning with a stressful.4-mA stimulus resulted in an increased frequency of dentate polysialylated neurons, the magnitude of which was indistinguishable from that observed following water maze training. By contrast, training with a traumatic 1-mA stimulus resulted in a significant decrease in the frequency of polysialylated neurons at the 12 hours posttraining time. Whereas sequential training in the water maze paradigm followed by fear conditioning resulted in potentiated consolidation of spatial information when conditioning involved a.4-mA stimulus, amnesia for spatial learning occurred when conditioning was performed with a 1-mA stimulus. CONCLUSIONS: These results suggest traumatic fear conditioning suppresses NCAM-PSA-mediated plasticity and the concomitant inability to store the trace of recently acquired information.
Asunto(s)
Condicionamiento Clásico , Giro Dentado/metabolismo , Miedo , Memoria , Moléculas de Adhesión de Célula Nerviosa/metabolismo , Neuronas/metabolismo , Percepción Espacial , Estrés Psicológico/metabolismo , Animales , Corticosterona/sangre , Estimulación Eléctrica , Inmunohistoquímica , Masculino , Aprendizaje por Laberinto , Ratas , Ratas Wistar , AguaRESUMEN
The impact was examined of exposing rats to two life experiences of a very different nature (stress and learning) on synaptic structures in hippocampal area CA3. Rats were subjected to either (i) chronic restraint stress for 21 days, and/or (ii) spatial training in a Morris water maze. At the behavioural level, restraint stress induced an impairment of acquisition of the spatial response. Moreover, restraint stress and water maze training had contrasting impacts on CA3 synaptic morphometry. Chronic stress induced a loss of simple asymmetric synapses [those with an unperforated postsynaptic density (PSD)], whilst water maze learning reversed this effect, promoting a rapid recovery of stress-induced synaptic loss within 2-3 days following stress. In addition, in unstressed animals a correlation was found between learning efficiency and the density of synapses with an unperforated PSD: the better the performance in the water maze, the lower the synaptic density. Water maze training increased the number of perforated synapses (those with a segmented PSD) in CA3, both in stressed and, more notably, in unstressed rats. The distinct effects of stress and learning on CA3 synapses reported here provide a neuroanatomical basis for the reported divergent effects of these experiences on hippocampal synaptic activity, i.e. stress as a suppressor and learning as a promoter of synaptic plasticity.
Asunto(s)
Hipocampo/fisiología , Aprendizaje por Laberinto/fisiología , Recuperación de la Función/fisiología , Estrés Fisiológico/fisiopatología , Sinapsis/fisiología , Animales , Conducta Animal , Hipocampo/ultraestructura , Masculino , Microscopía Electrónica , Ratas , Ratas Wistar , Restricción Física/métodos , Aprendizaje Inverso , Conducta Espacial , Sinapsis/ultraestructura , Factores de TiempoRESUMEN
We investigated whether contextual fear conditioning could be related to the behavioral trait of locomotor reactivity to novelty in undisturbed and chronically stressed rats. Fear conditioning was found to be specifically enhanced in low reactive-stressed animals, as compared to low reactive-undisturbed rats. The results suggest that individuals that display low reactivity to novelty are more susceptible to be influenced by stress exposure to subsequently exhibit potentiated contextual fear conditioning.
Asunto(s)
Condicionamiento Psicológico/fisiología , Conducta Exploratoria/fisiología , Miedo/fisiología , Individualidad , Estrés Fisiológico/fisiopatología , Animales , Enfermedad Crónica , Masculino , Ratas , Ratas WistarRESUMEN
Contextual fear conditioning under training conditions involving high stressor intensities has been proposed as an animal model for traumatic memories. The strength of memory for this task has been related to the intensity of the conditioning stressor and post-training corticosterone values. However, administration of a glucocorticoid receptor (GR) antagonist only attenuated memory for this task in rats conditioned at a moderate shock intensity (0.4 mA), but failed to influence conditioning in rats trained at a high shock intensity (1 mA). Here, we further questioned whether interfering with glucocorticoid action at the time of training might be effective in influencing contextual fear conditioning in rats trained under different shock intensities. Rats were subcutaneously injected with the glucocorticoid synthesis inhibitor metyrapone (50, 100 mg/kg) 90 min before being trained in the contextual fear conditioning task, at either 0.4 or 1 mA shock intensities. The results showed that metyrapone, in a dose-dependent manner: (i) attenuated long-term expression of contextual fear conditioning, both in 0.4- and 1 mA-trained rats; and (ii) efficiently prevented increased plasma corticosterone concentration. In addition to further supporting a facilitating role of glucocorticoids in memory consolidation, these findings suggest a critical involvement of these hormones in the formation of traumatic memories.