Changes In Emotional Reactivity Research Articles

Chronic retinyl palmitate supplementation to middle-aged Wistar rats disrupts the brain redox homeostasis and induces changes in emotional behavior.

Aging process makes older adults especially vulnerable to neurodegeneration and mental disorders. Overconsumption-related neurotoxic effects of certain dietary nutrients by older population could represent a contribution factor for the development of neuropsychiatric conditions by this subpopulation. Thus, we here investigated whether chronic supplementation with retinyl palmitate, at doses commonly found in vitamin supplements (300, 600, and 3000 mcg of RAE/kg/day), could have an impact on emotional behavior of middle-aged Wistar rats. We report that supplementation with retinyl palmitate for 28 days induces an altered emotional state of middle-aged Wistar rats and oxidative stress in cerebellum, cerebral cortex, hippocampus, and striatum, associated with imbalance of enzymatic antioxidant defenses, decrease in non-enzymatic antioxidant defenses, and increase in protein and lipid damages. Our data show evidence for (i) changes in emotional reactivity, similar to anxiety, in middle-aged rats chronically supplemented with retinyl palmitate; and (ii) suggest a possible interrelation between pro-oxidant events in the brain and these differences in the behavioral profile that cannot be attributed to hepatotoxicity. Our results invite for additional studies to further investigate such interrelation.

Changes in Emotional Reactivity and Distress Tolerance Among Heavy Drinking Adolescents During Sustained Abstinence

Negative affect and low distress tolerance have been associated with increased likelihood of alcohol consumption and relapse. This study utilized the Paced Auditory Serial Attention Test - Computerized Version (PASAT-C) to examine affective reactivity, cognitive performance, and distress tolerance during early abstinence among heavy drinking adolescents. Participants, ages 16 to 18 (50% female), were 23 heavy episodic drinking youth (HED) and 23 demographically matched, nondrinking teens (CON). Both groups were drawn from the same schools and assessed at 3 time points: HED was first studied within 10 days (M = 4.26, SD = 4.4) of heavy episodic drinking and then at two 2-week intervals over 4 subsequent weeks of abstinence from alcohol and drugs. CON were studied at the same 2-week intervals. From the findings, it was observed that HED responded with greater emotional response to the PASAT-C (i.e., greater increases in frustration and irritability and greater decreases in happiness) at the initial assessment, but their affective responses diminished with sustained abstinence. CON and HED task performance did not differ at the initial assessment or across time. HED showed faster task discontinuation times to the PASAT-C at the first assessment, and both groups reduced task persistence across testings. Among HED, greater lifetime and recent alcohol consumption, alcohol-induced blackouts, and withdrawal symptoms were associated with increases in negative affect with PASAT-C exposure. Earlier age of onset of alcohol use was linked to poorer performance. Heavy episodic drinking adolescents demonstrated heightened emotional reactivity and poorer distress tolerance to a cognitively challenging task during early abstinence. The combination of elevated negative affect and low distress tolerance may place adolescents at a heightened risk of escalations in or return to alcohol involvement.

Cognitive and emotional profiles of aged Alzheimer's disease (3×TgAD) mice: Effects of environmental enrichment and sexual dimorphism

Alzheimer's disease is a neurodegenerative disorder associated with age which represents the most common cause of dementia. It is characterized by an accelerated memory loss compared to normal aging, and deterioration of other cognitive abilities that interfere with mood, reason, judgment and language. The main neuropathological hallmarks of the disorder are β-amyloid (βA) plaques and neurofibrillary Tau tangles. Triple transgenic 3×TgAD mouse model develops βA and Tau pathologies in a progressive manner, with a specific temporal and anatomic profile mimicking the pattern that takes place in the human brain with AD, and showing cognitive alterations characteristic of the disease. Environmental enrichment treatment in mice induces behavioral and emotional reactivity changes, including cognitive improvements in some AD-related transgenic mice. The present work intended to characterize the behavioral profile of 3×TgAD mice at advanced stages of neuropathological development (12 and 15 months of age) and to investigate whether environmental enrichment administered during adulthood was able to modify some of their behavioral and cognitive alterations. Results show that, at advanced stages of the disease 3×TgAD mice show deficits of spatial learning acquisition, as well as short-term and working memory deficits, while displaying increased levels of anxiety/fearfulness and normal sensorimotor functions. 3×TgAD mice also show sexual dimorphism, as reflected by increased cognitive deficits in females and increased levels of novelty-induced behavioral inhibition in males. Environmental enrichment exerts some slight positive effects, by mainly improving the initial acquisition of the spatial learning and working memory in 12-month-old 3×TgAD mice. Such effects vary depending on the gender.

Emotions during live music performance: Links with individual differences in empathy, visual imagery, and mood.

Emotional responses to music involve the interplay of multiple factors related to music, listener, and situation (Gabrielsson, 2001; Scherer & Zentner, 2001). For instance, individuals differ in their capacity to understand and respond to the emotions they perceive in the environment (i.e., empathy), as well as to associate stimuli from any sensory modality with vivid images in the mind (i.e., visual imagery). Such stable individual differences (i.e., traits) may interact with more transient psychological characteristics (e.g., mood) and contextual features (e.g., location, the presence of others) in influencing emotional reactivity to music (Scherer & Coutinho, 2013). Therefore, real-life situations in which people come together to listen to music offer valuable opportunities to study the psychological underpinnings of emotional responses to music (Zentner & Eerola, 2010). The present study investigates the influence of individual differences in empathy, visual imagery, and mood on emotional responses to music during a live opera performance.Empathy and Visual Imagery in Music-Induced EmotionsProcess theories have identified empathy and visual imagery as two of the most important central or mechanisms by which music may induce emotions in listeners. For instance, Scherer and Zentner (2001) hypothesized that mirroring the emotions perceived in music through controlled and automatic processes of empathy, as well as associating music with images through memory-dependent processes of visual imagery are two important routes by which listeners may experience emotions in response to music (see also Garrido & Schubert, 2010; Scherer & Coutinho, 2013; Walton, 1999). These hypotheses were supported by the results of an experience-sampling study (Juslin, Liljestrom, Vastfjall, Barradas, & Silva, 2008), in which listeners identified emotional contagion (i.e., an automatic form of empathy; Hatfield, Cacioppo, & Rapson, 1993) and visual imagery as among the most important mechanisms by which music induced emotions in their everyday life. Following this study, a theoretical framework known as BRECVEM (i.e., an acronym for seven mechanisms by which music may induce emotions) was developed (Juslin, Liljestrom, Vastfjall, & Lundquist, 2010), which further emphasized the role of emotional contagion and visual imagery in emotional reactivity to music.Recent laboratory research supports the involvement of empathy and visual imagery in emotional reactivity to music. Several studies reported significant associations between listeners' trait empathy and their capacity to understand the expressive intentions of music performers (Wollner, 2012), as well as to develop emotions such as sadness or tenderness in response to music (Garrido & Schubert, 2011; Vuoskoski & Eerola, 2011a). The causal involvement of empathy in the generation of emotions to music was supported in an experiment in which the manipulation of empathy resulted in emotional reactivity changes to sad and joyful music, at the subjective and physiological levels (Miu & Baltes, 2012). There is indirect support for the link between visual imagery and music-induced emotions, given that empathy was assessed in several studies (Garrido & Schubert, 2011; Vuoskoski & Eerola, 2011a, 2012) using multidimensional measures that included imagination and fantasy subscales. Also, an experimental study using the Bonny Method of Guided Imagery and Music (Bonny, 1995) showed that encouraging participants to experience visual images during music listening improved mood and decreased basal cortisol (McKinney, Antoni, Kumar, Tims, & McCabe, 1997).Mood and Emotional Responses to MusicThe potential influence of listeners' background mood (i.e., a diffuse and relatively long affective state, often without apparent cause) has also been suggested in process theories of emotional responses to music (Scherer & Coutinho, 2013; Scherer & Zentner, 2001). …

Effects of complete vagotomy and blockage of cell adhesion molecules on interferon-α induced behavioral changes in mice

ObjectivesSickness behavior and chronic immune diseases are frequently associated with depressive symptomatology. In addition, immune activation by single cytokine therapies, such as treatment of malignancies and hepatitis C with interferon-alpha (IFN-α) often induces significant changes in emotional reactivity and affect. However, underlying pathogenic mechanisms of cytokine-induced brain dysfunction largely remain unknown. MethodsWe presently demonstrate the induction of anxiety- and depressive-like behavior in male BALB/c mice after prolonged treatment with murine IFN-α for up to four weeks. Subsequently, neural and cellular communication routes between the immune system and the brain were examined. ResultsIFN-α induced anxious and depressive-like behavior in a light dark, open field, tail suspension, and novel object paradigm with a maximum effect after two weeks of treatment. Effect sizes of IFN-α varied between variables from 23 to 41%. Behavioral deficits were not prevented by complete vagotomy, or by blocking leukocyte function-associated-1 (LFA-1)/intercellular adhesion molecule-1 (ICAM-1) and activated leukocyte cellular adhesion molecule (ALCAM)-mediated cellular adhesion events, which are both involved in immune cell entry to the brain. ConclusionsWe demonstrate emergence of anxiety- and depressive-like behavior in a mouse model of sustained IFN-α application allowing investigation of its pathogenic mechanisms, which is of clinical importance. We failed to demonstrate a critical effect for the vagus nerve or adhesion molecules, but current experiments do not allow excluding the vagus nerve as an afferent communication route. Future studies are needed to unveil if both pathways can be completely excluded in the etiology of behavioral deficits induced by IFN-α.

Pervasive alterations of emotional and neuroendocrine responses to an acute stressor after neonatal amygdala lesions in rhesus monkeys

The current study examined the long-term effects of neonatal amygdala lesions on emotional and hypothalamic-pituitary-adrenal (HPA) axis reactivity to an acute stressor in rhesus monkeys. Rhesus monkeys received either bilateral MRI-guided ibotenic acid amygdala (Neo-Aibo; n=6) or sham (Neo-C; n=7) lesions between 7 and 14 days of age. Emotional reactivity was assessed using the Human Intruder paradigm at 2 months, 4.5 months, and 6-8 years of age, whereas stress neuroendocrine response was only assessed in adulthood (6-8 years). The modulation of defensive and emotional behaviors based on the gaze direction of the intruder emerged between 2 and 4 months of age in surrogate-peer reared sham-operated infant monkeys, as already shown for mother-reared infants. Although neonatal amygdala lesions did not impair the ability to exhibit defensive and emotional behaviors, it altered the modulation of these responses based on the intruder's gaze direction. The changes in emotional reactivity after neonatal amygdala lesions emerged in infancy and persisted throughout adulthood when they were associated with a reduction of basal cortisol levels and a blunted cortisol response to the stressor. These changes are reminiscent of those found after adult-onset amygdala lesions, demonstrating little functional compensation following early amygdala damage.

The relation of developmental changes in brain serotonin transporter (5HTT) and 5HT1A receptor binding to emotional behavior in female rhesus monkeys: Effects of social status and 5HTT genotype

The goal of the present study was to examine how social subordination stress and 5HTT polymorphisms affect the development of brain serotonin (5HT) systems during the pubertal transition in female rhesus monkeys. We also examined associations with developmental changes in emotional reactivity in response to a standardized behavioral test, the Human Intruder (HI). Our findings provide the first longitudinal evidence of developmental increases in 5HT1A receptor and 5HTT binding in the brain of female primates from pre- to peripuberty. The increase in 5HT1A BPND in these socially housed female rhesus monkeys is a robust finding, occurring across all groups, regardless of social status or 5HTT genotype, and occurring in the left and right hemispheres of all prefrontal regions studied, as well as the amygdala, hippocampus, hypothalamus, and raphe nuclei. 5HTT BPND also showed an increase with age in raphe, anterior cingulate cortex, and dorsolateral prefrontal cortex. These changes in brain 5HT systems take place as females establish more adult-like patterns of social behavior, as well as during the HI paradigm. Indeed, the main developmental changes in behavior during the HI (increase in freezing and decrease in submission/appeasement) were related to neurodevelopmental increases in 5HT1A receptors and 5HTT, because the associations between these behaviors and 5HT endpoints emerge at peripuberty. We detected an effect of social status on 5HT1A BPND in the hypothalamus and on 5HTT BPND in the orbitofrontal cortex, with subordinates showing higher BPND than dominants in both cases during the pubertal transition. No main effects of 5HTT genotype were observed for 5HT1A or 5HTT BPND. Our findings indicate that adolescence in female rhesus monkeys is a period of central 5HT reorganization, partly influenced by exposure to the social stress of subordination, that likely functions to integrate adrenal and gonadal systems and shape the behavioral response to emotionally challenging social situations.

Control of sleep and wakefulness.

This review summarizes the brain mechanisms controlling sleep and wakefulness. Wakefulness promoting systems cause low-voltage, fast activity in the electroencephalogram (EEG). Multiple interacting neurotransmitter systems in the brain stem, hypothalamus, and basal forebrain converge onto common effector systems in the thalamus and cortex. Sleep results from the inhibition of wake-promoting systems by homeostatic sleep factors such as adenosine and nitric oxide and GABAergic neurons in the preoptic area of the hypothalamus, resulting in large-amplitude, slow EEG oscillations. Local, activity-dependent factors modulate the amplitude and frequency of cortical slow oscillations. Non-rapid-eye-movement (NREM) sleep results in conservation of brain energy and facilitates memory consolidation through the modulation of synaptic weights. Rapid-eye-movement (REM) sleep results from the interaction of brain stem cholinergic, aminergic, and GABAergic neurons which control the activity of glutamatergic reticular formation neurons leading to REM sleep phenomena such as muscle atonia, REMs, dreaming, and cortical activation. Strong activation of limbic regions during REM sleep suggests a role in regulation of emotion. Genetic studies suggest that brain mechanisms controlling waking and NREM sleep are strongly conserved throughout evolution, underscoring their enormous importance for brain function. Sleep disruption interferes with the normal restorative functions of NREM and REM sleep, resulting in disruptions of breathing and cardiovascular function, changes in emotional reactivity, and cognitive impairments in attention, memory, and decision making.

Short-term testosterone manipulations modulate visual recognition memory and some aspects of emotional reactivity in male rhesus monkeys

The role of testosterone (T) in modulating cognitive function and emotion in men remains unclear. The paucity of animal studies has likely contributed to the slow progress in this area. In particular, studies in nonhuman primates have been lacking. Our laboratory has begun to address this issue by pharmacologically manipulating T levels in intact male rhesus monkeys, using blind, placebo-controlled, crossover designs. We previously found that T-suppressed monkeys receiving supraphysiological T for 4weeks had lower visual recognition memory for long delays and enhanced attention to videos of negative social stimuli (Lacreuse et al., 2009, 2010) compared to when treated with oil. To further delineate the conditions under which T affects cognition and emotion, the present study focused on the short-term effects of physiological T. Six intact males were treated with the gonadotropin-releasing hormone antagonist degarelix (3mg/kg) for 7days and received one injection of T enanthate (5mg/kg) followed by one injection of oil vehicle 7days later (n=3), or the reverse treatment (n=3). Performance on two computerized tasks, the Delayed-non-matching-to-sample (DNMS) with random delays and the object-Delayed Recognition Span test (object-DRST) and one task of emotional reactivity, an approach/avoidance task of negative, familiar and novel objects, was examined at baseline and 3–5days after treatment. DNMS performance was significantly better when monkeys were treated with T compared to oil, independently of the delay duration or the nature (emotional or neutral) of the stimuli. Performance on the object-DRST was unaffected. Interestingly, subtle changes in emotional reactivity were also observed: T administration was associated with fewer object contacts, especially on negative objects, without overt changes in anxious behaviors. These results may reflect increased vigilance and alertness with high T. Altogether, the data suggest that changes in general arousal may underlie the beneficial effects of T on DNMS performance. This hypothesis will require further study with objective measures of physiological arousal.

Effects of modifying the interpretation of emotional ambiguity

People vary in how they perceive emotionally ambiguous events: For example, anxious individuals are particularly likely to interpret emotional ambiguity in a threatening way. Experimental studies have shown that such processing styles are malleable, and when modified can lead to corresponding changes in emotional reactivity. The methods used to modify processing and to assess subsequent changes in emotional reactivity are described and theoretical accounts of the mechanism underlying such changes are discussed. Recent application of related methods to modifying clinical problems demonstrates their utility, but beyond such practical applications, the approach provides new ways of probing the nature of the relationship between cognition and emotion.

The endocannabinoid system: a key modulator of emotions and cognition

The endocannabinoid system: a key modulator of emotions and cognition

Age-related differences in emotional reactivity, regulation, and rejection sensitivity in adolescence.

Although adolescents' emotional lives are thought to be more turbulent than those of adults, it is unknown whether this difference is attributable to developmental changes in emotional reactivity or emotion regulation. Study 1 addressed this question by presenting healthy individuals aged 10-23 with negative and neutral pictures and asking them to respond naturally or use cognitive reappraisal to down-regulate their responses on a trial-by-trial basis. Results indicated that age exerted both linear and quadratic effects on regulation success but was unrelated to emotional reactivity. Study 2 replicated and extended these findings using a different reappraisal task and further showed that situational (i.e., social vs. nonsocial stimuli) and dispositional (i.e., level of rejection sensitivity) social factors interacted with age to predict regulation success: young adolescents were less successful at regulating responses to social than to nonsocial stimuli, particularly if the adolescents were high in rejection sensitivity. Taken together, these results have important implications for the inclusion of emotion regulation in models of emotional and cognitive development.

Higher inherent fearfulness potentiates the effects of chronic stress in the Japanese quail

There is considerable variability in the susceptibility of individuals to the adverse effects of chronic stress. In humans and other mammals, individual traits such as high anxiety are proposed as a vulnerability factor for the development of stress-related disorders. In the present study, we tested whether a similar behavioural trait in birds, higher emotional reactivity, also favours the occurrence of chronic stress-related behavioural and physiological dysfunction. For this, lines of Japanese quail divergently selected for a typical fear response in birds, the duration of tonic immobility, were subjected to unpredictable aversive stimulation over 2 weeks. Previous studies demonstrate that the selection program modifies the general underlying emotionality of the birds rather than exerting its effect only on tonic immobility. Interestingly, only birds selected for their higher emotionality exhibited significantly enhanced latency to first step and decreased locomotor activity in the open-field test after exposure to chronic stress compared to non-stressed control birds. This effect of chronic stress was selective for the tested dimension of bird emotional reactivity because there was no observed effect on the tonic immobility response. Moreover, chronically stressed birds selected for their higher emotionality exhibited significantly decreased basal corticosterone levels, a physiological marker of stress. These findings show that chronic stress is associated with changes in emotional reactivity and related physiological markers in birds. They also highlight emotional reactivity as an important predisposing factor for the occurrence of the adverse effects of chronic stress in birds.

Psychobiological responses to unpleasant emotions in cannabis users

Aim of this paper is to investigate the psychobiological reactions to experimentally induced negative emotional states in active marijuana-dependent smokers and whether changes in emotional reactivity were reversed by prolonged abstinence. Twenty-eight patients were randomly included into group A (fourteen active marijuana-dependent smokers) or group B (fourteen abstinent marijuana-dependent subjects). Emotional response evaluation of group B subjects was assessed after 6months of abstinence. Fourteen healthy volunteers, matched for age and sex, were used as controls. Psychometric and emotional response evaluations were performed by administering Symptoms Check List-90 and State-Trait Anxiety Inventory Y-1 (STAI). Neutral and unpleasant set of pictures selected from the international affective picture system and the Self-Assesment Manikin procedure (SAM) have been used to determine ratings of pleasure and arousal. Before and after the experimental session, blood samples were collected to determine ACTH and cortisol plasma levels. Active cannabis users displayed significantly higher levels of pleasantness SAM scores and lower levels of arousal SAM scores compared to abstinent cannabis users and controls in response to emotional task. In a close parallel with psychological data, hormonal findings indicate a persistent hyperactivity of hypothalamus-pituitary-adrenal (HPA) axis in cannabis users, particularly among active marijuana smokers, and an impaired hormonal reaction to negative emotions, in comparison with healthy subjects. The capacity of the HPA axis to respond to stressful stimuli/negative emotions seems to be only partially recovered after 6months of abstinence. Ours findings, although obtained in a small number of subjects, suggest an association between active cannabis use, subjective reduced sensitivity to negative emotions and threat and HPA axis dysfunction.

Defining reactivity: How several methodological decisions can affect conclusions about emotional reactivity in psychopathology

There are many important methodological decisions that need to be made when examining emotional reactivity in psychopathology. In the present study, we examined the effects of two such decisions in an investigation of emotional reactivity in depression: (1) which (if any) comparison condition to employ; and (2) how to define change. Depressed (N = 69) and control (N = 37) participants viewed emotion-inducing film clips while subjective and facial responses were measured. Emotional reactivity was defined using no comparison condition (i.e., raw scores), baseline comparison condition (i.e., no stimulus presented), and neutral comparison condition (i.e., neutral stimulus presented). Change in emotional reactivity was assessed using four analytic approaches: difference scores, percentage change, residualised change, and ANCOVA. Results differed among the three comparison conditions and among several of the analytic approaches. Overall, our investigation suggests that choosing a comparison condition and the definition of change can significantly influence the presence of group differences in emotional reactivity. Recommendations for studies of emotional reactivity in psychopathology are discussed.

Increased emotional reactivity in rats following exposure to caffeine during adolescence

From 45 to 55 days after birth, male and female rats were treated via daily intraperitoneal injections with either isotonic saline, or 15 or 30 mg/kg caffeine. When 72–82 and 112–122 days old, their activity and emotional reactivity were assessed by means of frequencies of rearing, ambulation, immobility, defecation and urination recorded in an open field, as well as their occupancy of corners and center squares of the field, and their partial emergence and latencies to fully emerge from a small darkened chamber into a brightly lit arena. Rats treated with caffeine were probably more emotionally reactive than untreated controls as suggested by more immobility and defecation and urination. There were also effects on rearing and ambulation that might have arisen from increased impulsivity. Further evidence of caffeine treatment-induced higher emotional reactivity was found in the heavier adrenal glands of a small number of 10 months-old males. This occurred in the absence of any caffeine treatment effects on spatial reference memory measured by ability to identify a novel Y-maze arm. Changes between the two testing ages in rearing and emergence latencies, and sex-dependent changes in ambulation, defecation and corner and center squares occupancy, along with immobility for 30 mg/kg caffeine-treated subjects, were discussed in the light of possible changes in emotional reactivity. Sex differences in open-field rearing and ambulation, and testing age-dependent sex differences in corner and center squares occupancy were ascribed to higher emotional reactivity in males.

Neuropsychological Disorders Indicative of Postresuscitation Encephalopathy in Rats

The aim of this research was to study the effect of 12-minute clinical death on innate and acquired behavior, biogenic amine concentration, and the composition and quantity of neural populations in specific brain regions of white rats. The study shows that in animals during the postresuscitation period with formal restoration of neurological status, there are changes in emotional reactivity, orientation-exploration reactions, impairment of learning and memory, decrease in exercise tolerance and pain sensitivity. These processes are accompanied by alterations in serotonin and norepinephrine levels in the frontal cerebral cortex, dopamine and serotonin levels in the striatum, certain biochemical indices in blood plasma and neural loss in the CA1 sector of the hippocampus and lateral portions of the cerebellum.

Emotion Context Insensitivity in Major Depressive Disorder.

The present study tested 3 competing views of how depression alters emotional reactivity: positive attenuation (reduced positive), negative potentiation (increased negative), and emotion context insensitivity (ECI; reduced positive and negative). Normative and idiographic stimuli that elicited happy, sad, and neutral states were presented to currently depressed, formerly depressed, and healthy control individuals while experiential, behavioral, and autonomic responses were measured. Currently depressed individuals reported less sadness reactivity and less happiness experience across all conditions than did the other participants, and they exhibited a more dysphoric response to idiographic than to normative stimuli. Overall, data provide partial support for the positive attenuation and ECI views. Depression may produce mood-state-dependent changes in emotional reactivity that are most pronounced in emotion experience reports.

Neonatal novelty exposure ameliorates anoxia-induced hyperactivity in the open field

We investigated in an animal model of neonatal anoxia whether effects of oxygen deprivation on emotional reactivity can be reversed by neonatal novelty exposure, a behavioral method, involving daily 3 min away from the home cage for the first 3 weeks of life. Male neonates were exposed to either 100% N 2 gas (Anoxia) or room air (Control) for 25 min on postnatal day 1. Within each of the two treatment conditions, one-half of the neonates were further individually exposed to relatively novel non-home cages for 3 min daily during postnatal days 2–21 (Novel: N Anoxia = 20; N Control = 16), while the other half remained in the home cage (Home: N Anoxia = 19; N Control = 19). Emotional reactivity to an open field was evaluated on postnatal day 25 during four 20-s trials. Among home rats, temporal patterns of open-field activity across multiple trials and initial-trial activity significantly differed between the Anoxia and Control rats. In contrast, these differences were eliminated among the Novel rats. These results show that neonatal novelty exposure, an early-stimulation method that has recently been shown to enhance spatial and social memory, adaptive control of stress response, and hippocampal synaptic plasticity, can also eliminate neonatal anoxia-induced changes in emotional reactivity. These findings suggest that brief and repeated, but mild, changes in the postnatal environment may serve to counteract some of the aversive effects induced by neonatal trauma associated with oxygen deprivation.

Prenatal Exposure to the CB1 Receptor Agonist WIN 55,212-2 Causes Learning Disruption Associated with Impaired Cortical NMDA Receptor Function and Emotional Reactivity Changes in Rat Offspring

The aim of this study was to investigate whether prenatal exposure to the cannabinoid CB1 receptor agonist WIN 55,212-2 (WIN) at a daily dose devoid of overt signs of toxicity and/or gross malformations (0.5 mg/kg, gestation days 5-20), influences cortical glutamatergic neurotransmission, learning and emotional reactivity in rat offspring. Basal and K+-evoked extracellular glutamate levels were significantly lower in cortical cell cultures obtained from pups exposed to WIN during gestation with respect to those measured in cultures obtained from neonates born from vehicle-treated dams. The addition of NMDA to cortical cell cultures from neonates born from vehicle-treated dams concentration-dependently increased glutamate levels, and this was absent in cell cultures obtained from WIN-exposed pups. WIN-exposed rats also revealed a poorer performance in homing (10-12 days of age) and active avoidance tests (80 days of age) as well as a decrease in the rate of separation-induced ultrasonic emission (10 days of age). Finally, prenatal exposure to WIN induced a reduction in the number of cortical neuronal population. These findings (i) provide evidence for a deficit in cortical glutamatergic neurotransmission and behaviour in the rat neonate following prenatal exposure to WIN; and (ii) suggest that the reduction in cortical glutamatergic neurotransmission, NMDA receptor activity and alterations in neuronal development might underlie, at least in part, the learning deficit and decreased emotional reactivity observed in the offspring.