The environmental enrichment model revisited: A translatable paradigm to study the stress of our modern lifestyle.

Mounting evidence shows that physical activity, social interaction and sensorimotor stimulation provided by environmental enrichment (EE) exert several neurobehavioural effects traditionally interpreted as enhancements relative to standard housing (SH) conditions. However, this evidence rather indicates that SH induces many deficits, which could be ameliorated by exposing animals to an environment vaguely mimicking some features of their wild habitat. Rearing rodents in social isolation (SI) can aggravate such deficits, which can be restored by SH or EE. It is not surprising, therefore, that most preclinical stress models have included severe and unnatural stressors to produce a stress response prominent enough to be distinguishable from SH or SI-frequently used as control groups. Although current stress models induce a stress-related phenotype, they may fail to represent the stress of our urban lifestyle characterized by SI, poor housing and working environments, sedentarism, obesity and limited access to recreational activities and exercise. In the following review, we discuss the stress of living in urban areas and how exposures to and performing activities in green environments are stress relievers. Based on the commonalities between human and animal EE, we discuss how models of housing conditions (e.g., SI-SH-EE) could be adapted to study the stress of our modern lifestyle. The housing conditions model might be easy to implement and replicate leading to more translational results. It may also contribute to accomplishing some ethical commitments by promoting the refinement of procedures to model stress, diminishing animal suffering, enhancing animal welfare and eventually reducing the number of experimental animals needed.

Myocardial longitudinal strain, fitness, and heart failure risk factors in young adults.

AIMS: To investigate the relationship between fitness, heart failure (HF) risk factors (age, blood pressure, and obesity), and global/regional myocardial longitudinal strain in young adults undergoing stress testing. METHODS: Individuals 25-55 years old without any significant medical history, not taking medications, and with a normal maximal stress echocardiogram were eligible. Global and regional longitudinal strain (LS) was evaluated by 2D speckle tracking echocardiography. RESULTS: One hundred and seventy patients were included, of which 60% were males. The mean age was 43 years old, 49% had optimal blood pressure, and 30% were obese. On average, patients achieved 10.5 (3) METS, and the global LS was -19.9 (3.1) %. Reduced fitness was associated with decreased global longitudinal strain (GLS). Those in the top GLS quartile walked on average 1 minute and 21 seconds longer compared with the lowest quartile (P < .001). The effect of fitness on LS was preferential to the mid and apex, such that there was an apex-to-base gradient. Obesity was also independently associated with reduced GLS. However, the reduction in LS in obese individuals was more prominent at the base and mid-walls with relative sparing of the apex. Similar to fitness, aging was also associated with an increase in the apex-to-base gradient of LS. Furthermore, diastolic filling parameters correlated distinctively with regional LS. CONCLUSIONS: In young adults without cardiovascular disease, low fitness and obesity are independently associated with reduced left ventricular longitudinal strain. There is a differential effect of HF risk factors on regional longitudinal function.

Simplified prediction of postoperative cardiac surgery outcomes with a novel score: R2CHADS2.

OBJECTIVE: To compare the accuracy of R2CHADS2, CHADS2, and CHA2DS2-VASc scores vs the Society of Thoracic Surgeons (STS) score as predictors of morbidity and mortality after cardiovascular surgery. METHODS: All patients who underwent cardiothoracic surgery at our institution from January 2008 to July 2013 were analyzed. Only those patients who fulfilled the criteria for STS score calculation were included. The R2CHADS2 score was computed as follows: 2 points for GFR < 60 mL/min/1.73 m(2) (R2), prior stroke or TIA (S2); 1 point for history of congestive heart failure (C), hypertension (H), age ≥75 years (A), or diabetes (D). Area under the curve (AUC) analysis was used to estimate the accuracy of the different scores. The end point variables included operative mortality, permanent stroke, and renal failure as defined by the STS database system. RESULTS: Of the 3,492 patients screened, 2,263 met the inclusion criteria. These included 1,160 (51%) isolated valve surgery, 859 (38%) coronary artery bypass graft surgery, and 245 (11%) combined procedures. There were 147 postoperative events: 75 (3%) patients had postoperative renal failure, 48 (2%) had operative mortality, and 24 (1%) had permanent stroke. AUC analysis revealed that STS, R2CHADS2, CHADS2, and CHA2DS2-VASc reliably estimated all postoperative outcomes. STS and R2CHADS2 scores had the best accuracy overall, with no significant difference in AUC values between them. CONCLUSION: The R2CHADS2 score estimates postoperative events with acceptable accuracy and if further validated may be used as a simple preoperative risk tool calculator.

Age-dependent effects of environmental enrichment on spatial memory and neurochemistry.

Although aging and environmental stimulation are well-known to affect cognitive abilities, the question of whether aging effects can be distinguished in already-mature adult rats has not been fully addressed. In the present study, therefore, young and mature adult rats were housed in either enriched or standard conditions (EE or SC) for three months. Open-field (OFT) and radial-maze (RM) behavior, and ex-vivo contents of GABA and glutamate in hippocampus, and of dopamine and DOPAC in ventral striatum (VS) were analyzed and compared between the four groups. In OFT, young rats were more active than mature adults irrespective of the housing condition. Surprisingly, in the RM test, mature adults outperformed young counterparts except for the young-enriched rats, which showed a progressive improvement in RM performance. At the neurochemical level, young EE rats showed higher hippocampal glutamate and GABA concentrations, and DA turnover in VS, which correlated with RM performance. Altogether, the behavioral and cognitive strategies underlying habituation learning and spatial memory seem to be qualitatively different between the two ages analyzed. These results challenge the assumption that mature adult animals are always worse in learning and memory tasks. However, young rats benefited more from the social and physical stimulation provided by the enrichment than mature adult counterparts. The latter effect was evident not just on behavior, but also on brain neurochemistry.

Exploring the FAO Minimum Dietary Diversity Indicator as a Suitable Proxy of Micronutrient Adequacy in Men and Women Across Reproductive and Non-reproductive Ages in 8 Latin American Countries.

BACKGROUND: Women's Dietary Diversity Score (WDDS) is an indicator of dietary diversity, a key component of diet quality in women of reproductive age (WRA). Limited information is available regarding its applicability in other population groups. OBJECTIVE: To examine the ability of the Minimum Dietary Diversity for Women (MDD-W) of 5-food groups cutoff to predict micronutrient adequacy in men and women 15 to 65 years old from 8 Latin American countries. METHODS: We used a 24-hour recall from 9216 participants in the Latin American Study on Nutrition and Health (ELANS) to determine Dietary Diversity Score (DDS) based on the consumption of 10 food groups. The Mean Probability of Adequacy (MPA) was associated with DDS for the overall sample, for men, WRA, and women of nonreproductive age (WNRA). Sensitivity and specificity analyses were performed to determine if the 5-food groups cutoff point for MDD can be used to correctly identify men, WRA, and WNRA with adequate micronutrient adequacy (MPA ≥ 0.70). RESULTS: We found a mean DDS of 4.78 ± 1.33 and an MPA of 0.64 ± 0.16, with 59% of participants showing a diverse diet (DDS ≥ 5). The 5-food groups-cutoff point showed a better balance between sensitivity and specificity predicting an MPA ≥0.70 in men, WRA, and WNRA. MPA was significantly associated with DDS in WRA and for men and WNRA, as well. CONCLUSION: The 5-food group MDD, originally intended to be used in WRA, performed equally well in predicting MPA ≥0.70 in men, WRA, and WNRA, and can be used as a proxy of micronutrient adequacy in Latin American population.

Plain language titleAssessment of the FAO Minimum Dietary Diversity Index to Estimate Micronutrients Intake in Urban Cities of 8 Latin America CountriesPlain language summaryThe Women's Dietary Diversity Score (WDDS) proposed by the Food and Agriculture Organization is an indicator that measures the variety of foods consumed by women of reproductive age (WRA), and it has been reported in several studies that the more diverse the diet, the greater the probability of meeting micronutrients requirements. This indicator has not been validated in other population, but few studies have been conducted in the Latin American region. So, we aimed to investigate whether the Minimum Dietary Diversity for Women (MDD-W) established for WRA could also predict sufficient micronutrient intake in men and women aged 15 to 65 years in the Latin American population. To accomplish this objective, we used data from the Latin American Study of Nutrition and Health (Estudio Latino Americano de Nutrición y Salud­ELANS) that collected dietary data from 24-h recalls from 9216 participants and analyzed the association between DDS and the Mean Probability of Adequacy (MPA). Additionally, we determined if the MDD cutoff point could correctly identify individuals with appropriate vitamin and mineral intake. We found that the overall mean DDS was 4.78 ± 1.33, the MPA was 0.64 ± 0.16, and approximately 59% of participants had a diverse diet. The MDD of 5-food groups cutoff point was demonstrated to be useful in predicting sufficient micronutrient intake for men, WRA, and women over 50 years. Respondents with a DDS ≥5 had higher micronutrient adequacy. These findings suggest that DDS can serve as a proxy for assessing micronutrient adequacy in urban populations beyond WRA. The effect of promoting diverse diets on micronutrient adequacy as part of intervention programs can be captured by the DDS in urban Latin American populations.

Distinct acute stressors exert an antagonistic effect on complex grooming during novelty habituation in rats.

Grooming is a common readout in multiple rat models of neuropsychiatric diseases. It is usually associated with distress and negative emotionality, but also with emotional de-arousal after stress. These seemingly conflicting interpretations may result from specific grooming sequences appearing at different arousal levels and during distinct phases of the stress response. To further explore this hypothesis, we analyzed how distinct stressors affect grooming syntaxis and kinetics. To that end, we explored the independent and interacting effects of foot shocks, corticosterone (CORT), and novelty on exploratory activity, grooming, and ultrasonic vocalizations (USVs) in an open-field test (OF). Wistar rats were intraperitoneally injected either with vehicle or CORT, placed in a chamber where half of them were foot-shocked and then assessed in the OF. The next day, animals were re-exposed to the shock chamber and then tested in the OF without receiving any treatment. On day 1, foot shocks and -to a less extent CORT- increased freezing and inhibited rearing in the chamber, but only foot shocks increased distress USVs. In the OF, both treatments suppressed complex grooming, with foot-shocks also inhibiting exploration and CORT marginally reducing rearing. On day 2, foot-shocked rats showed conditioned fear when re-exposed to the chamber. When tested in the OF, foot-shocked and CORT-treated animals still showed low levels of complex grooming, with the former group also showing increased distress USVs. In this study, all different stressors inhibited complex grooming, suggesting an inverse association between these grooming subtypes and negative emotionality.

Time course of plasticity-related alterations following the first exposure to amphetamine in juvenile rats.

In vulnerable consumers, the first drug exposure induces various neurobehavioral adaptations that may represent the starting point toward addiction. Elucidating the neuroplastic mechanisms underlying that first rewarding experience would contribute to understanding the transition from recreational to compulsive drug use. In a preclinical model with juvenile rats, we analyzed the time-dependent fluctuations in the expression of neuroplasticity-related genes like the brain-derived neurotrophic factor (BDNF), its tropomyosin receptor kinase B (TrkB), the cAMP response element-binding protein (CREB), the microRNA-132, the Rho GTPase-activating protein 32 (p250GAP), the corticotropin-releasing factor (CRF), and the neurotransmitters contents in the nucleus accumbens (NAc) and the dorsal striatum (DS) 45, 90, and 180 min after an amphetamine (AMPH) injection. As expected, AMPH altered the concentration of norepinephrine, dopamine, DOPAC, and serotonin in a region- and time-dependent manner. Regarding gene expression, AMPH at 45 min upregulated BDNF and primiR-132 expression in NAc and downregulated TrkB expression in DS. At 90 min, AMPH upregulated TrkB, CREB, p250GAP, and primiR-132 expression in NAc and BDNF, primiR-132, and CRF in DS. At 180 min, only BNDF in NAc continued to be upregulated by AMPH. Based on the levels of AMPH-induced hyperactivity, we classified the rats as low and high AMPH responders. High AMPH responders characterized by overexpressing BDNF, CREB, p250GAP, and CRF in NAc and by showing lower levels of dopamine and serotonin metabolites and turnovers in both regions. Our findings demonstrated that a single AMPH administration is enough to induce neuroplastic adaptations, especially in the NAc of prone rats.

Muscarinic regulation of self-grooming behavior and ultrasonic vocalizations in the context of open-field habituation in rats.

Laboratory rats repeatedly exposed to an open field (OF) apparatus display increasingly high levels of grooming -especially that characterized by long and complex sequences- which has been taken as an additional index of novelty habituation. We hypothesized that disrupting such a learning process by administering an amnesic drug as the antimuscarinic scopolamine (SCP) could delay the appearance of more complex grooming subtypes. Thus, rats were pretreated either with SCP (15 mg/kg or 30 mg/kg) or vehicle (VEH) upon four one-day apart OF (OF1-4). On a fifth assessment, all rats received VEH to analyze the likely carry-over effect of SCP. Finally, we measured 50-kHz and 22-kHz ultrasonic vocalizations (USVs) as reliable markers of positive and negative emotionality, respectively. We found that SCP increased locomotion during OF1 and reduced rearing on OF1-OF4, causing no disruption in habituation over tests. SCP prevented the increase of total grooming time by inhibiting complex grooming subtypes and promoting short cephalic sequences. Despite the SCP-induced alterations on grooming agreed with our hypotheses, those changes may have resulted from a motor impairment that could have also affected rearing behavior. Additionally, SCP suppressed 50-kHz USVs while marginally increased 22-kHz calls. Once SCP was withdrawn, rearing, grooming, and some 50-kHz USVs subtypes returned to VEH levels, suggesting that novelty habituation occurred despite the SCP administration. Altogether, that mixed profile of SCP-induced behavioral changes may derive from the complex interplay between the contrasting action of SCP on different brain regions and the doses here used.

Fat Intake and Obesity-related Parameters Predict Striatal BDNF Gene Expression and Dopamine Metabolite Levels in Cafeteria Diet-fed Rats.

Modern westernized diet is a major risk factor associated with the current obesity epidemic. To study the effects of dietary choices of Western societies, the cafeteria diet has been validated as a preclinical model of obesity. We aimed to investigate the behavioral and metabolic alterations induced by a cafeteria diet on gene expression and neurotransmitter contents involved in neural plasticity and reward processing. Male Wistar rats were exposed to either standard or cafeteria diet for 9 weeks. Food intake and body weight were scored daily. Behavioral effects were assessed in the elevated plus-maze (EPM) and open field (OFT) tests. Serum biochemical parameters, brain monoamines, and BDNF, TrkB, CRF, CREB, and Dnmt3A mRNA levels were analyzed in reward-related brain regions. We found that cafeteria-diet rats consumed more energy and food than the control group, leading to increased body weight gain and adiposity. The cafeteria-diet rats showed an anxiolytic-like effect in the OFT, but not in the EPM. The cafeteria diet increased BDNF expression in the dorsal striatum (DS), and norepinephrine, 5-HT, TrkB, CREB, and Dnmt3A levels in the hippocampus. Additionally, multiple regression analysis showed that accumbal DOPAC and BDNF mRNA levels were robustly predicted by hyperphagia, fat mass accumulation, and body weight gain only in the cafeteria group. Overall, cafeteria diet-induced hyperphagia could lead to alterations in hedonic and motivational control of food intake through changes in dopamine metabolism and BDNF signaling in the nucleus accumbens and the DS.

Time-dependent changes in striatal monoamine levels and gene expression following single and repeated amphetamine administration in rats.

As drug addiction may result from pathological usurpations of learning and memory's neural mechanisms, we focused on the amphetamine-induced time-dependent neurochemical changes associated with neural plasticity. We used juvenile rats as the risk for drug abuse is higher during adolescence. Experiment 1 served to define the appropriate amphetamine dose and the neurochemical effects of a single administration. In experiment 2, rats received seven amphetamine or saline injections in the open-field test throughout a twelve-day period. We measured the mRNA levels of the brain-derived neurotrophic factor (BDNF), its tropomyosin receptor kinase B (TrkB), the cAMP response element-binding protein (CREB), the microRNA-132, the Rho GTPase-activating protein 32 (p250GAP), the corticotropin-releasing factor (CRF), and monoamines and amino-acids contents in the nucleus accumbens and the dorsal striatum 45, 90, and 180 min after the last injection. We found that amphetamine changed gene expression only at certain time points and in a dose and region-dependent manner. Repeated but not single administrations upregulated accumbal and striatal BDNF (180 min) and striatal pri-miR-132 (90 min) expression, while downregulated accumbal CREB levels (90 min). As only some drug users develop addiction, we compared brain parameters between low and high amphetamine responders. Prone subjects characterized by having reduced striatal 5-HT metabolism, higher accumbal BDNF and TrkB expression, and lower levels of CREB in the dorsal striatum and p250GAP in both regions. Thus, individual differences in drug-induced changes in neurotransmission and gene expression in nigrostriatal and mesolimbic dopaminergic pathways may underlie the plasticity adaptations associated with behavioral sensitization to amphetamine.

The cage test as an easy way to screen and evaluate spontaneous activity in preclinical neuroscience studies.

Within behavioral neuroscience, subjects used to be randomly assigned to the experimental groups based on the premise that interindividual variability will be homogeneously distributed. However, the equivalence offered by randomization diminishes in small samples, which is the case for most experiments in the field. In rodents, it is well-recognized that individual differences in psychomotor reactivity, risk-assessment behaviors, and emotional responsiveness modulate the effects of different pharmacological and non-pharmacological treatments. For that reason, knowing such differences before the experiment provides highly valuable information for balancing the groups so that the interindividual variability is equally distributed within the groups without excluding subjects as far as possible. Because unconditioned anxiety tests such as the open-field (OF) and the elevated plus-maze are commonly used within experimental procedures, we developed a strategy to explore the rat's behavioral phenotype by assessing it in a very innocuous testing context: a housing cage.•We offer a very straightforward protocol for assessing spontaneous, novelty-induced reactivity in rodents.•We describe its implementation, analysis, and use, as well as some suggestions about key behavioral readouts for the group allocation procedure.•The current protocol provides an alternative strategy to assess a reasonably wide range of behavioral outcomes, most of which are of great interest in modeling different neuropsychiatric disorders.

Acute stress differentially affects grooming subtypes and ultrasonic vocalisations in the open-field and home-cage test in rats.

Grooming behaviour in rodents has been associated with emotional distress, especially in unfamiliar and aversive contexts. However, the biological function of grooming in such situations is still unclear. We hypothesised that particular grooming subtypes are differentially associated with the stress response. Here, we investigated the effects of an acute stress exposure on grooming and ultrasonic vocalisations (USVs) assessed on different testing contexts varying in the level of familiarity. To this aim, footshocked and non-footshocked rats were tested for 20 min on one of the following conditions: an unfamiliar open-field test, a familiar open-field test, and an individual home cage filled with bedding. We found that footshock stress slightly decreased complex grooming sequences while increased cephalic grooming. Stress induced a negative affective state inferred from an increase and decrease of 22-kHz and 50-kHz calls, respectively. The latter USVs correlated positively with the complex grooming subtypes. Altogether, a detailed analysis of grooming seems necessary for elucidating its diverse biological functions. Nevertheless, footshock stress and testing conditions produced weaker-than-expected effects, possibly because the time elapsed between footshocks and behavioural testing was too short for eliciting a full stress response, and because the simple footshock-chamber experience may have impeded detecting stronger effects of familiarity.

Environmental Enrichment and Physical Exercise Attenuate the Depressive-Like Effects Induced by Social Isolation Stress in Rats.

We assessed the antidepressant-like effects of environmental enrichment (EE) and physical exercise (PE) compared with the selective serotonin reuptake inhibitor fluoxetine against the depression-related neurobehavioral alterations induced by postweaning social isolation (SI) in rats. After 1 month of SI, rats were submitted to PE (treadmill), EE, or fluoxetine (10 mg/kg), which were compared with naïve SI and group-housed rats. After 1 month, behavior was analyzed in the open field (OFT), the sucrose preference (SPT), and the forced swimming (FST) tests. Afterward, the hippocampal serotonin contents, its metabolite, and turnover were measured. SI induced a depression-related phenotype characterized by a marginal bodyweight gain, anxiety, anhedonia, behavioral despair, and alterations of serotonin metabolism. EE produced the widest and largest antidepressive-like effect, followed by PE and fluoxetine, which were almost equivalent. The treatments, however, affected differentially the neurobehavioral domains investigated. EE exerted its largest effect on anhedonia and was the only treatment inducing anxiolytic-like effects. Fluoxetine, in contrast, produced its largest effect on serotonin metabolism, followed by its anti-behavioral despair action. PE was a middle-ground treatment with broader behavioral outcomes than fluoxetine, but ineffective to reverse the serotonergic alterations induced by SI. The most responsive test to the treatments was the FST, followed closely by the SPT. Although OFT locomotion and body weight varied considerably between groups, they were barely responsive to PE and fluoxetine. From a translational standpoint, our data suggest that exercise and recreational activities may have broader health benefits than antidepressants to overcome confinement and the consequences of chronic stress.

Neurobehavioral Effects of Restricted and Unpredictable Environmental Enrichment in Rats.

To study how motivational factors modulate experience-dependent neurobehavioral plasticity, we modify a protocol of environmental enrichment (EE) in rats. We assumed that the benefits derived from EE might vary according to the level of incentive salience attributed to it. To enhance the rewarding properties of EE, access to the EE cage varied randomly from 2 to 48 h for 30 days (REE). The REE group was enriched only 50% of the time and was compared to standard housing and continuous EE (CEE) groups. As behavioral readout, we analyzed the spontaneous activity and the ultrasonic vocalizations (USVs) within the EE cage weekly, and in the open field test at the end of the experiment. In the cage, REE increased the utilization of materials, physical activity, and the rate of appetitive USVs. In the OF, the CEE-induced enhancements in novelty habituation and social signaling were equaled by the REE. At the neural level, we measured the expression of genes related to neural plasticity and epigenetic regulations in different brain regions. In the dorsal striatum and hippocampus, REE upregulated the expression of the brain-derived neurotrophic factor, its tropomyosin kinase B receptor, and the DNA methyltransferase 3A. Altogether, our results suggest that the higher activity within the cage and the augmented incentive motivation provoked by the REE boosted its neurobehavioral effects equaling or surpassing those observed in the CEE condition. As constant exposures to treatments or stimulating environments are virtually impossible for humans, restricted EE protocols would have greater translational value than traditional ones.

Age-dependent differences on neurochemistry and behavior in rats raised with low and high levels of maternal care.

In laboratory rats, naturally-occurring variations in maternal care have been used to study the neurobehavioral consequences of maternal nursing and to model the early-life adversity associated with many psychiatric disorders. This study aimed to determine the role of maternal care on behavior and monoamine concentrations at the prepubertal and young adulthood ages. We observed the licking/grooming (LG) behavior of Sprague-Dawley (SD) dams and assigned the litter to either low (LLG) or high (HLG) LG groups. Behavioral testing in the male offspring consisted of the open-field test, the elevated plus-maze, and the forced swimming test. Afterward, neurotransmitters contents were measured in the prefrontal cortex, the nucleus accumbens, the amygdala, and the hippocampus. We found that at the prepubertal stage, the effects of maternal care were only noticeable in the elevated plus-maze and the serotonin concentration in the nucleus accumbens. At adulthood, body weight and monoamines contents increased substantially in LLG rats. Specifically, they showed higher serotonin contents with a reduced turnover in almost all brain regions, followed by higher contents of norepinephrine and dopamine, especially in the nucleus accumbens. Changes in monoamines concentrations seem to be independent of the behavioral phenotype shaped by variations in maternal care, as behavioral effects were somewhat weak in both experiments. If higher monoamines contents in LLG rats represent an adaptive mechanism to deal with further adverse events, the behavioral paradigms used here were insufficiently challenging to bring out noticeable differences, at least in SD rats.

Effects of environmental enrichment and social isolation on sucrose consumption and preference: associations with depressive-like behavior and ventral striatum dopamine.

Little attention has been directed towards environmental control of sensitivity to natural reward and its possible relationship with other motivated behaviors, besides the well-known effects of environmental enrichment and social isolation on drug self-administration and locomotor sensitization to psychostimulants. Here, we investigate the effects of these rearing conditions on sucrose consumption and preference, and tissue levels of striatal dopamine. The possible relationship among sucrose intake, immobility behavior in the forced swimming test, and dopamine concentration was explored through correlation and regression analyses. Even though all animals preferred sucrose over water, we found, that during postnatal period, isolated rats consumed more sucrose than control or enriched littermates. In isolated rats sucrose intake correlated positively with ventral but not with dorsal striatum dopamine, even when striatal dopamine did not differ among groups. Especially in isolated animals immobility behavior was positively predicted by differences in sucrose intake. The dopamine concentration did not correlate with immobility behavior. Taken together, the present data support previous findings regarding the effects of early life events upon reward-sensitivity and depressive-like behavior, and also provide further evidence about the relationship between these motivated behaviors and the likely role of ventral striatum dopamine in regulating them.

Differential effect of environment enrichment and social isolation on depressive-like behavior, spontaneous activity and serotonin and norepinephrine concentration in prefrontal cortex and ventral striatum.

In order to determine the effect of postnatal environments on some behavioral and neurochemical depressive-like parameters, male Sprague-Dawley rats were reared from weaning in either social isolation, standard laboratory conditions, or environmental enrichment. Open-field activity was assessed at postnatal days 37, 65, 93 and 107 and 1 h before the last open-field test, a forced-swimming test was carried out. After behavioral tests, the monoamines concentrations were analyzed in prefrontal cortex and ventral striatum. Relative to control and isolation rearing, the environmental enrichment reduced open-field activity, led to antidepressive-like effects and increased serotonin concentrations in the prefrontal cortex. Social isolation, on the other hand, did not affect open-field activity, but increased depressive-like behavior and reduced the amount of norepinephrine in the ventral striatum. Those neurochemical changes induced by rearing conditions correlated with the behavioral performance in the forced-swimming test. Also, immobility behavior could be predicted by locomotor activity even from the first week of housing. Overall, specific variations in physical and social environment during early rearing lead to some behavioral and neurochemical alterations which might be relevant for understanding the role that neurodevelopmental and experiential factors could have in human depression.

Electrocardiographic Criteria for the Diagnosis of Left Ventricular Hypertrophy.

BACKGROUND: Current electrocardiographic (ECG) criteria for the diagnosis of left ventricular hypertrophy (LVH) have low sensitivity. OBJECTIVES: The goal of this study was to test a new method to improve the diagnostic performance of the electrocardiogram. METHODS: The study was divided into 2 groups, a test and a validation cohort. In the test cohort, 94 patients were analyzed, including 47 with the diagnosis of hypertensive crisis and 47 with normal blood pressure at admission. Echocardiography was used to estimate the left ventricular mass index. Area under the curve (AUC) analysis was used for comparison of single and combined leads. The McNemar test was used to assess agreement among the ECG criteria against the left ventricular mass index. The proposed ECG criteria involved measuring the amplitude of the deepest S wave (SD) in any single lead and adding it to the S wave amplitude of lead V4 (SV4). Currently accepted LVH ECG criteria such as Cornell voltage and Sokolow-Lyon were used for comparison. The validation cohort consisted of 122 consecutive patients referred for an echocardiogram regardless of the admitting diagnosis. RESULTS: The SD was the most accurate single lead measurement for the diagnosis of LVH (AUC: 0.80; p < 0.001). When both cohorts were analyzed, the SD + SV4 criteria outperformed Cornell voltage with a significantly higher sensitivity (62% [95% confidence interval [CI]: 50% to 72%] vs. 35% [95% CI: 24% to 46%]). The specificities of all the criteria were ≥90%, with no significant difference among them. CONCLUSIONS: The proposed criteria for the ECG diagnosis of LVH improved the sensitivity and overall accuracy of the test.

Differential effects of social and physical environmental enrichment on brain plasticity, cognition, and ultrasonic communication in rats.

Environmental enrichment (EE) exerts beneficial effects on brain plasticity, cognition, and anxiety/depression, leading to a brain that can counteract deficits underlying various brain disorders. Because the complexity of the EE commonly used makes it difficult to identify causal aspects, we examined possible factors using a 2 × 2 design with social EE (two vs. six rats) and physical EE (physically enriched vs. nonenriched). For the first time, we demonstrate that social and physical EE have differential effects on brain plasticity, cognition, and ultrasonic communication. Expectedly, physical EE promoted neurogenesis in the dentate gyrus of the hippocampal formation, but not in the subventricular zone, and, as a novel finding, affected microRNA expression levels, with the activity-dependent miR-124 and miR-132 being upregulated. Concomitant improvements in cognition were observed, yet social deficits were seen in the emission of prosocial 50-kHz ultrasonic vocalizations (USV) paralleled by a lack of social approach in response to them, consistent with the intense world syndrome/theory of autism. In contrast, social EE had only minor effects on brain plasticity and cognition, but led to increased prosocial 50-kHz USV emission rates and enhanced social approach behavior. Importantly, social deficits following physical EE were prevented by additional social EE. The finding that social EE has positive whereas physical EE has negative effects on social behavior indicates that preclinical studies focusing on EE as a potential treatment in models for neuropsychiatric disorders characterized by social deficits, such as autism, should include social EE in addition to physical EE, because its lack might worsen social deficits.

Individual differences in anticipatory activity to food rewards predict cue-induced appetitive 50-kHz calls in rats.

Reward-related stimuli come to acquire incentive salience through Pavlovian learning and become capable of controlling reward-oriented behaviors. Here, we examined individual differences in anticipatory activity elicited by reward-related cues as indicative of how animals attribute incentive salience to otherwise neutral stimuli. Since adult rats can signal incentive motivation states through ultrasonic vocalizations (USVs) at around 50-kHz, such calls were recorded in food-deprived rats trained to associate cues with food rewards, which were subsequently devalued by satiation.We found that the extent to which animals developed conditioned anticipatory activity to food cues while food deprived determined the level of cue-induced appetitive USVs while sated. Re-exposure to reward cues after a free-testing period reinstated USVs, invigorated reward seeking and consumption, and again, increases in calling occurred only in animals with high levels of cue-induced anticipatory activity. Reward-experienced rats systemically challenged with the catecholamine agonist amphetamine or with the dopamine receptor antagonist flupenthixol showed attenuated responses to these drugs, especially for USVs and in subjects with high levels of cue-induced anticipatory activity. Our results suggest that individuals prone to attribute incentive salience to reward cues showed heightened reward-induced USVs which were reliably expressed over time and persisted despite physiological needs being fulfilled. Also, prone subjects seemed to undergo particular adaptations in their dopaminergic system related with incentive learning. Our findings may have translational relevance in preclinical research modeling compulsive disorders, which may be due to excessive attribution of incentive salience to reward cues, such as overeating, pathological gambling, and drug addiction.