The hippocampus, neurotrophic factors and depression: possible implications for the pharmacotherapy of depression.: Depression is a prevalent, highly debilitating mental disorder affecting up to 15% of the population at least once in their lifetime, with huge costs for society. Neurobiological mechanisms of depression are still not well known, although there is consensus about interplay between genetic and environmental factors. Antidepressant medications are frequently used in depression, but at least 50% of patients are poor responders, even to more recently discovered medications. Furthermore, clinical res
Neuroplasticity and brain change
The brain changing with experience and practice.
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المكتبة البحثية677 works heldPeer-reviewed work held with its DOI and abstract, labelled with the study design its publication types report. None of it has been read or assessed, so nothing here may be cited as showing anything. Retracted work is held for the record but never listed; a review that a later version replaced is listed under its replacement and marked.
Orexins/hypocretins control bistability of hippocampal long-term synaptic plasticity through co-activation of multiple kinases.: Aim: Orexins/hypocretins (OX/Hcrt) are hypothalamic neuropeptides linking sleep-wakefulness, appetite and neuroendocrine control. Their role and mechanisms of action on higher brain functions, such as learning and memory, are not clear. Methods: We used field recordings of excitatory post-synaptic potentials (fEPSP) in acute mouse brain slice preparations to study the effects of orexins and pharmacological inhibitors of multiple kinases on long-term synaptic plasticity in the hippocampus. Result
Exergaming and older adult cognition: a cluster randomized clinical trial.: Background: Dementia cases may reach 100 million by 2050. Interventions are sought to curb or prevent cognitive decline. Exercise yields cognitive benefits, but few older adults exercise. Virtual reality-enhanced exercise or "exergames" may elicit greater participation. Purpose: To test the following hypotheses: (1) stationary cycling with virtual reality tours ("cybercycle") will enhance executive function and clinical status more than traditional exercise; (2) exercise effort will explain impr
Serotonin affects transcranial direct current-induced neuroplasticity in humans.: Background: Modulation of the serotonergic system affects long-term potentiation (LTP) and long-term depression (LTD), the likely neurophysiologic derivates of learning and memory formation, in animals and slice preparations. Serotonin-dependent modulation of plasticity has been proposed as an underlying mechanism for depression. However, direct knowledge about the impact of serotonin on neuroplasticity in humans is missing. Here we explore the impact of the serotonin reuptake blocker citalopram
A systematic review and meta-analysis of clinical studies on major depression and BDNF levels: implications for the role of neuroplasticity in depression.: Several clinical studies on major depressive disorder (MDD) have shown that blood brain-derived neurotrophic factor (BDNF) - a factor used to index neuroplasticity - is associated with depression response; however, the results are mixed. The purpose of our study was to evaluate whether BDNF levels are correlated with improvement of depression. We performed a systematic review and meta-analysis of the literature, searching Medline, Cochrane Central, SciELO databases and reference lists from retri
Neuroplasticity - exercise-induced response of peripheral brain-derived neurotrophic factor: a systematic review of experimental studies in human subjects.: Exercise is known to induce a cascade of molecular and cellular processes that support brain plasticity. Brain-derived neurotrophic factor (BDNF) is an essential neurotrophin that is also intimately connected with central and peripheral molecular processes of energy metabolism and homeostasis, and could play a crucial role in these induced mechanisms. This review provides an overview of the current knowledge on the effects of acute exercise and/or training on BDNF in healthy subjects and in pers
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551 to 575 of 677Altered anterior insula activation during anticipation and experience of painful stimuli in expert meditators.
Experientially opening oneself to pain rather than avoiding it is said to reduce the mind's tendency toward avoidance or anxiety which can further exacerbate the experience of pain. This is a central feature of mindfulness-based therapies. Little is known about the neural mechanisms of mindfulness on pain. During a meditation practice similar to mindfulness, functional magnetic resonance imaging was used in expert meditators (>10,000 h of practice) to dissociate neural activation patterns associated with pain, its anticipation, and habituation. Compared to novices, expert meditators reported equal pain intensity, but less unpleasantness. This difference was associated with enhanced activity in the dorsal anterior insula (aI), and the anterior mid-cingulate (aMCC) the so-called 'salience network', for experts during pain. This enhanced activity during pain was associated with reduced base…
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Mice heterozygous for the oxytocin receptor gene (Oxtr(+/-)) show impaired social behaviour but not increased aggression or cognitive inflexibility: evidence of a selective haploinsufficiency gene effect.
We characterised the behavioural phenotype of mice heterozygous (Oxtr(+/-)) for the oxytocin receptor gene (Oxtr) and compared it with that of Oxtr null mice (Oxtr(-/-)), which display autistic-like behaviours, including impaired sociability and preference for social novelty, impaired cognitive flexibility, and increased aggression. Similar to Oxtr(-/-) mice, the Oxtr(+/-) showed impaired sociability and preference for social novelty but, unlike the null genotype, their cognitive flexibility and aggression were normal. By autoradiography, Oxtr(+/-) mice were found to have approximately 50% fewer oxytocin receptors (OXTRs) in all of the examined brain regions. Thus, because a partial reduction in Oxtr gene expression is sufficient to compromise social behaviour, the Oxtr acts as a haploinsufficient gene. Furthermore, the inactivation of the Oxtr gene affects specific behaviours in a dose-…
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Increased gray matter volume in the right angular and posterior parahippocampal gyri in loving-kindness meditators.
Previous voxel-based morphometry (VBM) studies have revealed that meditation is associated with structural brain changes in regions underlying cognitive processes that are required for attention or mindfulness during meditation. This VBM study examined brain changes related to the practice of an emotion-oriented meditation: loving-kindness meditation (LKM). A 3 T magnetic resonance imaging (MRI) scanner captured images of the brain structures of 25 men, 10 of whom had practiced LKM in the Theravada tradition for at least 5 years. Compared with novices, more gray matter volume was detected in the right angular and posterior parahippocampal gyri in LKM experts. The right angular gyrus has not been previously reported to have structural differences associated with meditation, and its specific role in mind and cognitive empathy theory suggests the uniqueness of this finding for LKM practice.…
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Functional brain connectivity at rest changes after working memory training.
Networks of functional connectivity are highly consistent across participants, suggesting that functional connectivity is for a large part predetermined. However, several studies have shown that functional connectivity may change depending on instructions or previous experience. In the present study, we investigated whether 6 weeks of practice with a working memory task changes functional connectivity during a resting period preceding the task. We focused on two task-relevant networks, the frontoparietal network and the default network, using seed regions in the right middle frontal gyrus (MFG) and the medial prefrontal cortex (PFC), respectively. After practice, young adults showed increased functional connectivity between the right MFG and other regions of the frontoparietal network, including bilateral superior frontal gyrus, paracingulate gyrus, and anterior cingulate cortex. In addi…
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On the generalised embodiment of pain: how interoceptive sensitivity modulates cutaneous pain perception.
Individual differences in interoceptive sensitivity are associated with differences in reported intensity of emotional experience, vulnerability to anxiety and mood disorder and capacity for emotional self-regulation. Enhanced sensitivity to autonomic state is often accompanied by increased autonomic reactivity. Here we tested the hypothesis that healthy people classified as more interoceptively sensitive, by their performance of a heartbeat monitoring task, will demonstrate enhanced perception of pain. We further explored whether this effect is associated with a greater physiological reactivity to the pain stimuli. Using an algometer, cutaneous pressure pain was applied to the thenar eminence in 60 healthy participants. Heart rate variability and respiratory activity were recorded concurrently. We observed significant relationships between heightened interoceptive sensitivity and both e…
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Sleep oscillations in the thalamocortical system induce long-term neuronal plasticity.
Long-term plasticity contributes to memory formation and sleep plays a critical role in memory consolidation. However, it is unclear whether sleep slow oscillation by itself induces long-term plasticity that contributes to memory retention. Using in vivo prethalamic electrical stimulation at 1 Hz, which itself does not induce immediate potentiation of evoked responses, we investigated how the cortical evoked response was modulated by different states of vigilance. We found that somatosensory evoked potentials during wake were enhanced after a slow-wave sleep episode (with or without stimulation during sleep) as compared to a previous wake episode. In vitro, we determined that this enhancement has a postsynaptic mechanism that is calcium dependent, requires hyperpolarization periods (slow waves), and requires a coactivation of both AMPA and NMDA receptors. Our results suggest that long-te…
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Emotion regulation and brain plasticity: expressive suppression use predicts anterior insula volume.
Expressive suppression is an emotion regulation strategy that requires interoceptive and emotional awareness. These processes both recruit the anterior insula. It is not known, however, whether increased use of expressive suppression is associated with increased anterior insula volume. In the present study, high-resolution anatomical MRI images were used to calculate insula volumes in a set of 50 healthy female subjects (mean 21.9 years) using both region of interest (ROI) and voxel-based morphometry (VBM) approaches. Participants also completed trait measures of expressive suppression usage, cognitive reappraisal usage, and negative emotional reactivity (the latter two served as control measures). As predicted, both ROI and VBM methods found that expressive suppression usage, but not negative affect and cognitive reappraisal, was positively related to anterior insula volume. These findi…
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Reversing pathological neural activity using targeted plasticity.
Brain changes in response to nerve damage or cochlear trauma can generate pathological neural activity that is believed to be responsible for many types of chronic pain and tinnitus. Several studies have reported that the severity of chronic pain and tinnitus is correlated with the degree of map reorganization in somatosensory and auditory cortex, respectively. Direct electrical or transcranial magnetic stimulation of sensory cortex can temporarily disrupt these phantom sensations. However, there is as yet no direct evidence for a causal role of plasticity in the generation of pain or tinnitus. Here we report evidence that reversing the brain changes responsible can eliminate the perceptual impairment in an animal model of noise-induced tinnitus. Exposure to intense noise degrades the frequency tuning of auditory cortex neurons and increases cortical synchronization. Repeatedly pairing t…
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Intermittent ethanol consumption depresses endocannabinoid-signaling in the dorsolateral striatum of rat.
Recent research suggests that adaptations elicited by drugs of abuse share common features with traditional learning models, and that drugs of abuse cause long-term changes in behavior by altering synaptic function and plasticity. In this study, endocannabinoid (eCB) signaling in the dorsolateral striatum, a brain region vital for habit formation, was evaluated in acutely isolated brain slices from ethanol (EtOH)-consuming rats and control rats. EtOH-consuming rats had free access to a 20% EtOH solution for three 24 hour sessions a week during seven weeks and consumed an average of 3.4 g/kg per session. eCB-mediated long-lasting disinhibition (DLL) of population spike (PS) amplitude induced by moderate frequency stimulation was impaired in EtOH-consuming rats, and was not restored by the muscarinic receptor antagonist scopolamine (10 μM). The lack of DLL could be linked to a reduced GABA…
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Frontostriatal involvement in task switching depends on genetic differences in d2 receptor density.
Recent studies suggest an association of dopamine D2 receptor (DRD2) availability with flexibility in reward-based learning. We extend these results by demonstrating an association of genetically based differences in DRD2 density with the ability to intentionally switch between nonrewarded tasks: noncarriers of the A1 allele of the DRD2/ANKK1-TaqIa polymorphism, associated with higher DRD2 density, show increased task-switching costs, increased prefrontal switching activity in the inferior frontal junction area, and increased functional connectivity in dorsal frontostriatal circuits, relative to A1 allele carriers. A DRD2 haplotype analysis in the same sample confirmed these results, indicating an association between high D2 density and increased task-switching effort. Our results provide evidence that converges with that from association studies relating increased D2 density to deficits…
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Cognitive impairment in pain through amygdala-driven prefrontal cortical deactivation.
Cognitive deficits such as impaired decision-making can be a consequence of persistent pain. Normal functions of the intact amygdala and prefrontal cortex are required for emotion-based decision-making that relies on the ability to assess risk, attribute value, and identify advantageous strategies. We tested the hypothesis that pain-related cognitive deficits result from amygdala-driven impairment of medial prefrontal cortical (mPFC) function. To do this, we used electrophysiological single-unit recordings in vivo, patch clamp in brain slices, and various behavioral assays to show that increased neuronal activity in the amygdala in an animal model of arthritis pain was accompanied by decreased mPFC activation and impaired decision-making. Furthermore, pharmacologic inhibition (with a corticotropin-releasing factor 1 receptor antagonist) of pain-related hyperactivity in the basolateral am…
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Training of working memory impacts structural connectivity.
Working memory is the limited capacity storage system involved in the maintenance and manipulation of information over short periods of time. Individual capacity of working memory is associated with the integrity of white matter in the frontoparietal regions. It is unknown to what extent the integrity of white matter underlying the working memory system is plastic. Using voxel-based analysis (VBA) of fractional anisotropy (FA) measures of fiber tracts, we investigated the effect of working memory training on structural connectivity in an interventional study. The amount of working memory training correlated with increased FA in the white matter regions adjacent to the intraparietal sulcus and the anterior part of the body of the corpus callosum after training. These results showed training-induced plasticity in regions that are thought to be critical in working memory. As changes in myel…
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Reconsolidation: maintaining memory relevance.
The retrieval of a memory places it into a plastic state, the result of which is that the memory can be disrupted or even enhanced by experimental treatment. This phenomenon has been conceptualised within a framework of memories being reactivated and then reconsolidated in repeated rounds of cellular processing. The reconsolidation phase has been seized upon as crucial for the understanding of memory stability and, more recently, as a potential therapeutic target in the treatment of disorders such as post-traumatic stress and drug addiction. However, little is known about the reactivation process, or what might be the adaptive function of retrieval-induced plasticity. Reconsolidation has long been proposed to mediate memory updating, but only recently has this hypothesis been supported experimentally. Here, the adaptive function of memory reconsolidation is explored in more detail, with …
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Cutting your nerve changes your brain.
Following upper limb peripheral nerve transection and surgical repair, some patients regain good sensorimotor function while others do not. Understanding peripheral and central mechanisms that contribute to recovery may facilitate the development of new therapeutic interventions. Plasticity following peripheral nerve transection has been demonstrated throughout the neuroaxis in animal models of nerve injury. However, the brain changes that occur following peripheral nerve transection and surgical repair in humans have not been examined. Furthermore, the extent to which peripheral nerve regeneration influences functional and structural brain changes has not been characterized. Therefore, we asked whether functional changes are accompanied by grey and/or white matter structural changes and whether these changes relate to sensory recovery? To address these key issues we (i) assessed periphe…
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Emotion regulation in spider phobia: role of the medial prefrontal cortex.
Phobic responses are strong emotional reactions towards phobic objects, which can be described as a deficit in the automatic regulation of emotions. Difficulties in the voluntary cognitive control of these emotions suggest a further phobia-specific deficit in effortful emotion regulation mechanisms. The actual study is based on this emotion regulation conceptualization of specific phobias. The aim is to investigate the neural correlates of these two emotion regulation deficits in spider phobics. Sixteen spider phobic females participated in a functional magnetic resonance imaging (fMRI) study in which they were asked to voluntarily up- and down-regulate their emotions elicited by spider and generally aversive pictures with a reappraisal strategy. In line with the hypothesis concerning an automatic emotion regulation deficit, increased activity in the insula and reduced activity in the ve…
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Stress-induced dendritic remodeling in the prefrontal cortex is circuit specific.
Chronic stress exposure has been reported to induce dendritic remodeling in several brain regions, but it is not known whether individual neural circuits show distinct patterns of remodeling. The current study tested the hypothesis that the projections from the infralimbic (IL) area of the medial prefrontal cortex (mPFC) to the basolateral nucleus of the amygdala (BLA), a pathway relevant to stress-related mental illnesses like depression and post-traumatic stress disorder, would have a unique pattern of remodeling in response to chronic stress. The retrograde tracer FastBlue was injected into male rats' BLA or entorhinal cortex (EC) 1 week prior to 10 days of immobilization stress. After cessation of stress, FastBlue-labeled and unlabeled IL pyaramidal neurons were loaded with fluorescent dye Lucifer Yellow to visualize dendritic arborization and spine density. As has been previously re…
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Grey and white matter distribution in very preterm adolescents mediates neurodevelopmental outcome.
Very preterm (VPT) birth is associated with altered cortical development and long-term neurodevelopmental sequelae. We used voxel-based morphometry to investigate white (WM) and grey matter (GM) distribution in VPT adolescents and controls, and the association with gestational age and neonatal ultrasound findings in the VPT individuals. GM and WM volumes were additionally investigated in relation to adolescent neurodevelopmental outcome. Structural MRI data were acquired with a 1.5 Tesla machine in 218 VPT adolescents (<33 weeks, gestation) and 128 controls aged 14-15 years, and analysed using SPM2 software. VPT individuals compared to controls showed reduced GM in temporal, frontal, occipital cortices and cerebellum, including putamen, insula, cuneus, fusiform gyrus, thalamus and caudate nucleus, and increased GM predominantly in temporal and frontal lobes, including cingulate and fusif…
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Sleep in children improves memory performance on declarative but not procedural tasks.
Sleep supports the consolidation of memory in adults. Childhood is a period hallmarked by huge demands of brain plasticity as well as great amounts of efficient sleep. Whether sleep supports memory consolidation in children as in adults is unclear. We compared effects of nocturnal sleep (versus daytime wakefulness) on consolidation of declarative (word-pair associates, two-dimensional [2D] object location), and procedural memories (finger sequence tapping) in 15 children (6-8 yr) and 15 adults. Beneficial effects of sleep on retention of declarative memories were comparable in children and adults. However, opposite to adults, children showed smaller improvement in finger-tapping skill across retention sleep than wakefulness, indicating that sleep-dependent procedural memory consolidation depends on developmental stage.
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Increase in prefrontal cortical volume following cognitive behavioural therapy in patients with chronic fatigue syndrome.
Chronic fatigue syndrome (CFS) is a disabling disorder, characterized by persistent or relapsing fatigue. Recent studies have detected a decrease in cortical grey matter volume in patients with CFS, but it is unclear whether this cerebral atrophy constitutes a cause or a consequence of the disease. Cognitive behavioural therapy (CBT) is an effective behavioural intervention for CFS, which combines a rehabilitative approach of a graded increase in physical activity with a psychological approach that addresses thoughts and beliefs about CFS which may impair recovery. Here, we test the hypothesis that cerebral atrophy may be a reversible state that can ameliorate with successful CBT. We have quantified cerebral structural changes in 22 CFS patients that underwent CBT and 22 healthy control participants. At baseline, CFS patients had significantly lower grey matter volume than healthy contro…
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Daytime naps, motor memory consolidation and regionally specific sleep spindles.
Background: Increasing evidence demonstrates that motor-skill memories improve across a night of sleep, and that non-rapid eye movement (NREM) sleep commonly plays a role in orchestrating these consolidation enhancements. Here we show the benefit of a daytime nap on motor memory consolidation and its relationship not simply with global sleep-stage measures, but unique characteristics of sleep spindles at regionally specific locations; mapping to the corresponding memory representation. Methodology/principal findings: Two groups of subjects trained on a motor-skill task using their left hand - a paradigm known to result in overnight plastic changes in the contralateral, right motor cortex. Both groups trained in the morning and were tested 8 hr later, with one group obtaining a 60-90 minute intervening midday nap, while the other group remained awake. At testing, subjects that did not nap…
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Attending to the present: mindfulness meditation reveals distinct neural modes of self-reference.
It has long been theorised that there are two temporally distinct forms of self-reference: extended self-reference linking experiences across time, and momentary self-reference centred on the present. To characterise these two aspects of awareness, we used functional magnetic resonance imaging (fMRI) to examine monitoring of enduring traits ('narrative' focus, NF) or momentary experience ('experiential' focus, EF) in both novice participants and those having attended an 8 week course in mindfulness meditation, a program that trains individuals to develop focused attention on the present. In novices, EF yielded focal reductions in self-referential cortical midline regions (medial prefrontal cortex, mPFC) associated with NF. In trained participants, EF resulted in more marked and pervasive reductions in the mPFC, and increased engagement of a right lateralised network, comprising the later…
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Changes in activity of the striatum during formation of a motor habit.
To examine experience-dependent plasticity of striatal neurons during habit learning in awake, freely moving animals, single neurons in the dorsolateral striatum (54 neurons related specifically to vertical head movement and 14 unresponsive neurons, i.e. not related to any body movement) were recorded and tracked off-line to assess changes in firing rate over sessions as performance of instrumental head movement became automatic and habitual. Rats were trained to emit operant vertical head movements that triggered water delivery for 14 sessions (2 h per session, one session per day). Rats significantly increased the number and efficiency of head movements over sessions until reaching asymptotic behaviour. Habit formation was indicated by significantly higher levels of instrumental responding exhibited by rats during a late, relative to an early, session in which the reward was devalued. …
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Genetic manipulation of intraspinal plasticity after spinal cord injury alters the severity of autonomic dysreflexia.
Severe spinal cord injuries above mid-thoracic levels can lead to a potentially life-threatening hypertensive condition termed autonomic dysreflexia, which is often triggered by painful distension of pelvic viscera (bladder or bowel) and consequent sensory fiber activation, including nociceptive C-fibers. Interruption of tonically active medullo-spinal pathways after injury causes disinhibition of thoracolumbar sympathetic preganglionic neurons, and intraspinal sprouting of nerve growth factor (NGF)-responsive primary afferent fibers is thought to contribute to their hyperactivity. We investigated spinal levels that are critical for eliciting autonomic dysreflexia using a model of noxious colorectal distension (CRD) after complete spinal transection at the fourth thoracic segment in rats. Post-traumatic sprouting of calcitonin gene-related peptide (CGRP)-immunoreactive primary afferent f…
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Drug addiction: the neurobiology of disrupted self-control.
The nature of addiction is often debated along moral versus biological lines. However, recent advances in neuroscience offer insights that might help bridge the gap between these opposing views. Current evidence shows that most drugs of abuse exert their initial reinforcing effects by inducing dopamine surges in limbic regions, affecting other neurotransmitter systems and leading to characteristic plastic adaptations. Importantly, there seem to be intimate relationships between the circuits disrupted by abused drugs and those that underlie self-control. Significant changes can be detected in circuits implicated in reward, motivation and/or drive, salience attribution, inhibitory control and memory consolidation. Therefore, addiction treatments should attempt to reduce the rewarding properties of drugs while enhancing those of alternative reinforcers, inhibit conditioned memories and stre…
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Stress history and pubertal development interact to shape hypothalamic-pituitary-adrenal axis plasticity.
Both the magnitude and the duration of the hormonal stress response change dramatically during neonatal development and aging as well as with prior experience with a stressor. However, surprisingly little is known with regard to how pubertal maturation and experience with stress interact to affect hypothalamic-pituitary-adrenal axis responsiveness. Because adolescence is a period of neurodevelopmental vulnerabilities and opportunities that may be especially sensitive to stress, it is imperative to more fully understand these interactions. Thus, we examined hormonal and neural responses in prepubertal (28 d of age) and adult (77 d of age) male rats after exposure to acute (30 min) or more chronic (30 min/d for 7 d) restraint stress. We report here that after acute stress, prepubertal males exhibited a significantly prolonged hormonal stress response (e.g. ACTH and total and free corticost…
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