Exploring the role of environmental enrichment and early life adversity on emotional development.

Early life adversity has been linked with a higher probability of developing behavioral impairments and environmental manipulation is a strategy that may reduce the negative effects of exposure to adversity in early life. Here, we focused on exploring the influence of environmental enrichment (EE) as a protective factor in the context of early life adversity. We hypothesized that 24 hours of maternal deprivation (MD), in the second week of life, could induce anxiety-like behavior alterations and that exposure to EE could induce resilience to these behaviors due to alterations in the serotonergic system. Male Wistar rats were exposed to MD, on postnatal days 11 and 13, and to EE, after weaning. In adulthood, we performed a series of behavioral tests for fear, anxiety, and locomotor activity. We also measured the levels of serotonin in the amygdala and dorsal raphe nucleus. Our results revealed that MD does not impact fear behavior or the levels of serotonin, while EE decreases locomotor activity in a novel environment and enhances exploration in the predator odor test. EE also decreases serotonin in the amygdala and increases its turnover rate levels. Our findings provide insights into the critical timeframe during which stress exposure impacts the development and confirm that exposure to EE has an independent and protective effect for anxiety-like behaviors later in life.

Early life stress and the programming of eating behavior and anxiety: Sex-specific relationships with serotonergic activity and hypothalamic neuropeptides.

Early life experiences have strong influences on brain programming and can affect eating behavior control and body weight later in life. However, there is no consensus about the relationship between neonatal stress and feeding behavior. We evaluated whether maternal deprivation (MD) and maternal separation (MS) alter body weight and appetite using standard rat chow consumption and palatable food. Also, we evaluated anxiety and the expression of the leptin receptor, neuropeptides POMC, CART, NPY in the hypothalamus, as well as the serotoninergic system in the amygdala and hypothalamus as possible modulators of these behaviors. We found a decrease in standard rat chow consumption in MD. However, both neonatal stress protocols increased the consumption of palatable food and led to anxiogenic behavior in male animals. MD led to decreased hypothalamic POMC levels in adult males. Serotonin in the hypothalamus was decreased by both stress models in males and females. In the amygdala, MS decreased serotonin levels while MD increased its metabolite levels. We observed that males are more vulnerable and females are more resilient to the effects of neonatal stress on anxiety-like behavior, as well as on food consumption and on the central changes observed. These data together add support to the concept that the early environment contributes to the development of eating disorders later in life.

Correction: Testosterone deficiency reduces the effects of late cardiac remodeling after acute myocardial infarction in rats.

[This corrects the article DOI: 10.1371/journal.pone.0213351.].

Testosterone deficiency reduces the effects of late cardiac remodeling after acute myocardial infarction in rats.

Testosterone is associated with an increased risk of coronary heart disease. This study evaluated cardiac remodeling 60 days after myocardial infarction (MI) in rats with testosterone deficiency. One week after castration, the animals underwent myocardial infarction. Rats were divided into four groups: orchidectomized (OCT); orchidectomized and infarcted (OCT+MI), MI and control (Sham). The myocyte cross-sectional area and the papillary muscle contractility were evaluated 8 weeks after MI. The coronary bed was perfused with Biodur E20 resin to evaluate the neovascularization after MI. Data were expressed as mean ± SEM followed by ANOVA. Castration reduced myocyte hypertrophy when compared to Sham and myocardial infarction alone as well as preserved the contraction force and activation time after myocardial infarction. After beta-adrenergic stimulation, activation and relaxation kinetics were less impaired in the OCT+MI group than in the MI group. Contraction force was preserved in the OCT+MI group after beta-adrenergic stimulation. Multiple scanning electronic microscope images were obtained to characterize changes in the coronary arteries. Capillary density index was increased in the MI and OCT+MI groups compared with control. The MI and OCT+MI groups were characterized by irregular vessel arrangements with distorted shape, abrupt changes in vessel direction, as well as abrupt changes in diameter after bifurcations when compared to Sham and OCT. The results indicated that testosterone deficiency attenuates adverse cardiac remodeling after MI. Novel findings in this study were that testosterone deficiency in rats, induced by castration, changes the later remodeling after MI, when compared with non castrated rats. The absence of this androgenous hormone seems to be benefic against pathological hypertrophy.

Short-term full kindling of the amygdala dissociates natural and periaqueductal gray-evoked flight behaviors of the rat.

Panic attacks present a high comorbidity with agoraphobia, separation anxiety and generalized anxiety disorder. Nevertheless, while panic attacks have been frequently equated to fear, the relationship of panic disorder with specific phobias remains uncertain. The combination of experimental models of panic and phobias could but afford valuable information about both the comorbidity and causation of these disorders. As it regards, while the defensive behaviors produced by stimulation of dorsal periaqueductal gray matter (DPAG) resemble a panic attack, resistance to capture (RC) behaviors that ensue the kindling of the amygdala (AMY) are reminiscent of a phobic reaction. Therefore, this study examined the thresholds of DPAG-evoked panic-like behaviors in rats showing RC behaviors. Rats bearing electrodes in the DPAG and right AMY were subjected to either the full- (Kin-F) or sham- (Kin-S) kindling of AMY. RC behaviors were evaluated throughout both kindling procedures. Thresholds of DPAG-evoked defensive behaviors were recorded before and after the kindling. Moreover, performances of Kin-F and Kin-S rats in the elevated plus-maze were compared to those of intact controls. Data showed that Kin-F and Kin-S rats perform similarly in the elevated plus-maze, thereby making AMY-kindled rats unlikely as a model of generalized anxiety disorder. On the other hand, whereas the RC is characterized by a marked facilitation of natural freezing and flight behaviors, DPAG-evoked freezing (immobility and exophthalmus) and flight (galloping) behaviors were unexpectedly attenuated. Data suggest that RC is mediated by circuits distinct from those of DPAG-evoked defensive behaviors. Consequently, panic and phobic attacks may be mediated by different mechanisms as well.