Does Environmental Enrichment Reduce Stress? An Integrated Measure of Corticosterone from Feathers Provides a Novel Perspective

Enrichment is widely used as tool for managing fearfulness, undesirable behaviors, and stress in captive animals, and for studying exploration and personality. Inconsistencies in previous studies of physiological and behavioral responses to enrichment led us to hypothesize that enrichment and its removal are stressful environmental changes to which the hormone corticosterone and fearfulness, activity, and exploration behaviors ought to be sensitive. We conducted two experiments with a captive population of wild-caught Clark's nutcrackers (Nucifraga columbiana) to assess responses to short- (10-d) and long-term (3-mo) enrichment, their removal, and the influence of novelty, within the same animal. Variation in an integrated measure of corticosterone from feathers, combined with video recordings of behaviors, suggests that how individuals perceive enrichment and its removal depends on the duration of exposure. Short- and long-term enrichment elicited different physiological responses, with the former acting as a stressor and birds exhibiting acclimation to the latter. Non-novel enrichment evoked the strongest corticosterone responses of all the treatments, suggesting that the second exposure to the same objects acted as a physiological cue, and that acclimation was overridden by negative past experience. Birds showed weak behavioral responses that were not related to corticosterone. By demonstrating that an integrated measure of glucocorticoid physiology varies significantly with changes to enrichment in the absence of agonistic interactions, our study sheds light on potential mechanisms driving physiological and behavioral responses to environmental change

Effect of environmental enrichment on stress related systems in rats

The aim of this study was to test whether environmental enrichment alters the status and responsiveness of pituitary-adrenocortical and sympathetic-adrenomedullary hormones in rats. Previous studies have shown that rats kept in an enriched environment differ from those kept in standard cages in dendritic branching, synaptogenesis, memory function, emotionality and behaviour. In male Wistar rats kept in an enriched environment for 40 days, we studied basal concentrations of hormones, endocrine responses to 5-HT1A challenge and responsiveness and adaptation to repeated handling. Environmental enrichment consisted of large plexiglass cages with 10 rats per cage, which contained variety of objects exchanged three times a week. Rats kept in this enriched environment had higher resting plasma concentrations of corticosterone, larger adrenals and increased corticosterone release to buspirone challenge compared to controls. Lower adrenocorticotropic hormone, corticosterone and adrenaline responses to handling were noticed in rats kept in an enriched environment. Exposure to repeated handling led to a more rapid extinction of corticosterone responses in rats kept in an enriched environment. Thus, environmental enrichment leads to pronounced changes in neuroendocrine regulation, including larger adrenals and increased adrenocortical function, which are so far considered to be indication of chronic stress

Modulation of neuroendocrine response and non-verbal behavior during psychosocial stress in healthy volunteers by the glutamate release-inhibiting drug lamotrigine

The present work was aimed at verifying the following hypotheses: (a) lamotrigine, a drug used to treat mood disorders, affects regulation of stress hormone release in humans, and (b) non-verbal behavior during mental stress situations (public speech) is related to hormonal responses. To achieve these aims, we performed a controlled, double-blind study investigating hormonal responses and non-verbal behavior during public speech in healthy subjects with placebo or lamotrigine (300 mg per os) pretreatment. The stress procedure was performed in 19 young healthy males 5 h following drug or placebo administration. Data were obtained from cardiovascular monitoring, blood and saliva samples, as well as the video-recorded speech. Pre-stress hormone levels were not affected by lamotrigine treatment. Lamotrigine significantly inhibited diastolic blood pressure, growth hormone and cortisol increases during psychosocial stress. In contrast, it potentiated plasma renin activity and aldosterone responses. Non-verbal behavior analysis revealed a correlation between catecholamines and submissive or flight behavior in controls, while between catecholamines and displacement behavior following lamotrigine administration. In conclusion, effects of lamotrigine on hormone release might be of value for its mood-stabilizing action used in the treatment of bipolar disorder. The data are in support of a stimulatory role of glutamate in the control of cortisol and growth hormone release during psychosocial stress in humans; however, further studies using more selective drugs are needed to prove this suggestion. The effects on plasma renin activity and aldosterone release observed seem to be related to other actions of lamotrigine

Voluntary wheel running modulates glutamate receptor subunit gene expression and stress hormone release in Lewis rats

Lewis rats that are known to be addiction-prone, develop compulsive running if they have access to running wheels. The present experiments were aimed 1) to evaluate the activation of stress systems following chronic and acute voluntary wheel running in Lewis rats by measurement of hormone release and gene expression of neuropeptides related to hypothalamic-pituitary-adrenocortical (HPA) axis activity and 2) to test the hypothesis that wheel running as a combined model of addictive behavior and stress exposure is associated with modulation of ionotropic glutamate receptor subunits in the ventral tegmental area. Voluntary running for three weeks but not for one night resulted in a rise in plasma corticosterone and adrenocorticotropic hormone (ACTH) levels (p < 0.05) compared to those in control rats. Principal component analysis revealed the relation between POW gene expression in the intermediate pituitary and running rate. Acute exposure of animals to voluntary wheel running induced a significant decrease in alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionate (AMPA) receptor GluR1 subunit mRNA levels (p < 0.01), while repeated voluntary physical activity increased levels of GluR1 mRNA in the ventral tegmentum (P < 0.05). Neither acute nor chronic wheel running influenced N-methyl-D-aspartate (NMDA) receptor subunit NR1 mRNA levels in the ventral tegmental area. Thus, the present study revealed changes in AMPA receptor subunit gene expression in a reward-related brain structure as well as an activation of HPA axis in response to compulsive wheel running in Lewis rats. It may be suggested that hormones of HPA axis and glutamate receptors belong to the factors that substantiate higher vulnerability to addictive behavior. (C) 2003 Elsevier Science Ltd. All rights reserved

Involvement of glutamate neurotransmission in the development of excessive wheel running in Lewis rats

Physical activities such as long-distance running can form a habit and might be related to drug-induced addictive behaviors. We investigated possible modulations of N-methyl-D-aspartate (NMDA) receptor subunits during voluntary wheel running in brain regions implicated in reward and addiction. It was observed that Lewis rats progressively increased their amount of daily running, reaching maximum levels of 4-6 km/day. After 3 weeks of running, mRNA levels coding for NR2A and NR2B subunits were increased in the ventral tegmental area, while only NR2A mRNA levels were found to be elevated in the frontal cortex. Long-term wheel running was also associated with increased binding of specific NMDA receptor antagonist [H-3]CGP39653 in the frontal cortex. Moreover, pharmacological inhibition of glutamate release by repeated administration of phenytoin (20 mg/kg IP for 21 days) significantly suppressed daily running. These results suggest that glutamatergic neurotransmission might be related to neurobiological mechanisms underlying the compulsive character of voluntary wheel running