Chronic foot shock induces hyperactive behaviors and accompanying pro- and anti-inflammatory responses in mice.
ABSTRACT Behavioral and accompanying physiological and immunological changes were investigated at various times during chronic irregular mild foot shock (CMFS) in adult male BALB/c mice. CMFS induced a significant hyperlocomotor activity in a familiar environment as well as increased consumption of chocolate milk (a favored drink) throughout the 5-week stress period. Unlike other chronic stress models, CMFS did not induce depressive-like behaviors. Hyperactivity was associated with transient elevations of pro-inflammatory cytokines (TNFalpha and IL-1beta) and IL-2 and more sustained (IL-10) or later (arginase activity) elevations in anti-inflammatory mediators in the spleen (serum levels below levels of detection) suggesting a transition from a pro-inflammatory state to an anti-inflammatory state during CMFS. Similar increases in brain levels of IL-2 and arginase activity were also detected and may contribute to CMFS-induced hyperactivity as both of these mediators have been shown to induce hyperactivity. To our knowledge, this is the first time that increased arginase activity has been documented during a stress paradigm. Altogether, the data indicate that CMFS induces behavioral changes distinct from other chronic stress models. CMFS is associated with multiple dynamic immunological changes, suggesting involvement of multiple factors in chronic stress-induced behavioral changes.
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ABSTRACT: Experimental stress has been shown to have analgesic as well as allodynic effect in animals. Despite the obvious negative influence of stress in clinical pain conditions, stress-induced alteration of pain sensitivity has not been tested in humans so far. Therefore, we tested changes of pain sensitivity using an experimental stressor in ten female healthy subjects and 13 female patients with fibromyalgia. Multiple sensory aspects of pain were evaluated in all participants with the help of the quantitative sensory testing protocol before (60 min) and after (10 and 90 min) inducing psychological stress with a standardized psychosocial stress test ("Trier Social Stress Test"). Both healthy subjects and patients with fibromyalgia showed stress-induced enhancement of pain sensitivity in response to thermal stimuli. However, only patients showed increased sensitivity in response to pressure pain. Our results provide evidence for stress-induced allodynia/hyperalgesia in humans for the first time and suggest differential underlying mechanisms determining response to stressors in healthy subjects and patients suffering from chronic pain. Possible mechanisms of the interplay of stress and mediating factors (e.g. cytokines, cortisol) on pain sensitivity are mentioned. Future studies should help understand better how stress impacts on chronic pain conditions.PLoS ONE 01/2013; 8(8):e69460. · 3.73 Impact Factor
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ABSTRACT: The present study was designed to examine behavioral responses (interpreted as preferences) to olfactory cues (nest bedding odor and odors of estrous and anestrus females) in adult male rats after they had had a short term reversible, bilateral, nasal obstruction (RbNO) as developing rat pups. These results were compared to behavior of control (untreated) and sham operated male littermates. Behavioral tests and physiological parameters were analyzed 90 days after recovery of nasal breathing. Experiments investigated the time spent in arms or the centre of a maze of male rats in response to odors from the nest bedding or from adult females. There were no differences in responses between untreated, sham and RbNO adult male rats to fresh and nest bedding odors. RbNO males spent more time in the centre of the maze when given a choice of estrus or anestrus female odors, or bedding odors from untreated or sham operated female rats. In contrast untreated and sham male rats preferred the odors of estrous females and of untreated or sham females. Plasma corticosterone levels in the males increased during the behavioral tests. Plasma testosterone levels were significantly lower in RbNO males compared to untreated males and did not increase during the behavioral tests compared to sham operated males. Males from all groups had similar preferences for the odor of bedding from adult RbNO females. Plasma levels of cholesterol and triglycerides were increased in RbNO adults. In conclusion, short term nasal obstruction in males while juvenile has long term consequences on hormones and behavioral preferences, thus potential partner selection when adult.Brain research bulletin 04/2014; · 2.18 Impact Factor
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ABSTRACT: Although increasing evidence demonstrates that both chronic stressors and inflammatory immune activation contribute to pathophysiology and behavioral alterations associated with major depression, little is known about the interaction effect of central inflammatory immune activation and stress on depressive-like behavior. Our previous work has shown that 14-day chronic forced swim stress induces significant depressive-like behavior. The present investigation assessed whether pro-inflammatory cytokine and anti-inflammatory cytokine challenges have differential interaction effect on depressive-like behavior induced by chronic forced swim stress in rats. The pro-inflammatory and anti-inflammatory immune challenges were achieved respectively by central administration of lipopolysaccharide (LPS), a pro-inflammatory cytokine inducer, and interleukin-10 (IL-10), an anti-inflammatory cytokine. It was found that either central LPS treatment alone or chronic forced swim stress alone significantly induced depressive-like behavior, including reduced body weight gain, reduced saccharin preference and reduced locomotor activity. However, there was no significant synergistic or additive effect of central LPS treatment and stress on depressive-like behavior. LPS treatment did not exacerbate the depressive-like behavior induced by forced swim stress. Nevertheless, IL-10 reversed depressive-like behavior induced by forced swim stress, a finding indicating that IL-10 has antidepressant effect on behavioral depression induced by stress. The present findings provide new insight into the complexity of the immunity-inflammation hypothesis of depression.Behavioural brain research 03/2013; · 3.22 Impact Factor