Effects Of Footshock Stress Research Articles

Effects of footshock stress on social behavior and neuronal activation in the medial prefrontal cortex and amygdala of male and female mice.

Social behavior is complex and fundamental, and its deficits are common pathological features for several psychiatric disorders including anxiety, depression, and posttraumatic stress disorder. Acute stress may have a negative impact on social behavior, and these effects can vary based on sex. The aim of this study was to explore the effect of acute footshock stress, using analogous parameters to those commonly used in fear conditioning assays, on the sociability of male and female C57BL/6J mice in a standard social approach test. Animals were divided into two main groups of footshock stress (22 male, 24 female) and context exposed control (23 male and 22 female). Each group had mice that were treated intraperitoneally with either the benzodiazepine-alprazolam (control: 10 male, 10 female; stress: 11 male, 11 female), or vehicle (control: 13 male, 12 female; stress: 11 male, 13 female). In all groups, neuronal activation during social approach was assessed using immunohistochemistry against the immediate early gene product cFos. Although footshock stress did not significantly alter sociability or latency to approach a social stimulus, it did increase defensive tail-rattling behavior specifically in males (p = 0.0022). This stress-induced increase in tail-rattling was alleviated by alprazolam (p = 0.03), yet alprazolam had no effect on female tail-rattling behavior in the stress group. Alprazolam lowered cFos expression in the medial prefrontal cortex (p = 0.001 infralimbic area, p = 0.02 prelimbic area), and social approach induced sex-dependent differences in cFos activation in the ventromedial intercalated cell clusters (p = 0.04). Social approach following stress-induced cFos expression was positively correlated with latency to approach and negatively correlated with sociability in the prelimbic area and multiple amygdala subregions (all p < 0.05). Collectively, our results suggest that acute footshock stress induces sex-dependent alterations in defensiveness and differential patterns of cFos activation during social approach.

A mouse model of stress-enhanced fear learning demonstrates extinction-sensitive and extinction-resistant effects of footshock stress

Stressful experiences can cause long-lasting sensitization of fear and anxiety that extends beyond the circumstances of the initial trauma. The neural mechanisms of these stress effects have been studied extensively in rats using the stress-enhanced fear learning (SEFL) paradigm, in which exposure to footshock stress potentiates subsequent fear conditioning. Here we establish a mouse version of the SEFL paradigm. Male and female 129s6 mice received four 1-mA footshocks or equivalent context exposure without shock. Shock exposure induced Pavlovian fear conditioning to the shock context and produced three more general effects: (1) suppression of open field exploration, (2) potentiated unconditioned fear of a novel tone stimulus, and (3) enhanced fear conditioning in a novel context. To determine whether these effects of footshock stress reflect generalized Pavlovian fear conditioning versus nonassociative fear sensitization, some mice received extinction training in the footshock stress context, which reduced contextual fear to the levels of unstressed control mice. Extinction restored normal open field exploration, suggesting that this effect of stress reflects generalized Pavlovian fear. In contrast, extinction failed to attenuate stress-enhanced fear, indicating that stress-enhanced fear is nonassociative and mechanistically distinct from Pavlovian fear conditioning. The effects of footshock stress were similar in male and female mice, although female mice displayed larger acute responses to fear-inducing stimuli than did males. The results demonstrate that footshock stress influences emotional behavior through distinct associative and nonassociative mechanisms, which likely involve unique neural underpinnings.

Apoptosis status from rat heart submitted to foot shock stress

ABSTRACT Background and aim: The goal of this study was to investigate whether physical stress is able to modulate apoptotic response in rat myocardial tissue. The effects of foot shock stress on the histopatological changes and immunohistochemistry for p53, bcl‐2 and bax were evaluated. Methods: Male Wistar rats (n= 10) were distributed into two groups: group 1, control and group 2, stress. The stress protocol consisted of one daily foot‐shock session applied on three consecutive days. Results: The results pointed out no remarkable changes of myocardial tissue between groups. Also, the foot shock stress was not able to modulate p53, bcl‐2 or bax expression, as depicted by no significant statistically differences (P &gt; 0.05) between groups for all immunomarkers evaluated. Conclusions: Taken together, our results suggest that foot shock stress did not induce histopathological changes in rat myocardial tissue. It seems that physical stress is not able to modulate apoptotic response in rats. Certainly, this finding offers new insights into the mechanisms underlying the relation between apoptosis and cardiac injury after stress.

Acute mild footshock alters ethanol drinking and plasma corticosterone levels in C57BL/6J male mice, but not DBA/2J or A/J male mice

Stress is an often-reported cause for alcohol consumption in humans. Acute intermittent footshock is a frequently used paradigm to produce stress in laboratory animals including mice. The effect produced by intermittent footshock stress on ethanol self-administration has been inconsistent: both increases and decreases in ethanol consumption have been reported. The current set of studies further investigates, in three commonly studied mouse strains, the effect of footshock stress on ethanol self-administration. Furthermore, the effect of footshock on plasma corticosterone levels was determined to investigate potential biochemical correlates. Adult male C57BL/6J, DBA/2J, and A/J mice were allowed to self-administer 10% (wt/vol) ethanol for 12 days in a standard 23-h two-bottle paradigm before receiving either 15 min of mild inescapable footshock or no footshock. Shock intensity was equal to the mean intensity at which each strain vocalized as previously determined. Following footshock, animals had the opportunity to self-administer ethanol for an additional 23 h. Separate animals were subjected to either footshock or no shock prior to collection of plasma for corticosterone. Mild footshock stress altered ethanol self-administration and increased plasma corticosterone levels in C57BL/6J mice. Footshock stress did not alter ethanol self-administration or plasma corticosterone levels in DBA/2J or A/J mice. These data demonstrate that mild footshock stress is a suboptimal method of modeling the stress-induced increases in ethanol consumption often reported by humans.

Intra-median raphe nucleus (MRN) infusions of muscimol, a GABA-A receptor agonist, reinstate alcohol seeking in rats: role of impulsivity and reward

We previously found that the inhibition of median raphe nucleus (MRN) 5-HT transmission by local injections of a 5-HT1A agonist 8-OH-DPAT or corticotrophin-releasing factor (CRF) mimic the effect of foot shock stress to reinstate alcohol seeking. In this study, we further explored the role of the MRN by examining the effect of inhibition of MRN neurons, by injecting the GABA-A receptor agonist muscimol, on the reinstatement of alcohol seeking. Male rats were trained to lever press for 12% alcohol. Cannulae were implanted aimed at the MRN; some rats were also given intra-MRN injections of 5,7-DHT to destroy ascending 5-HT neurons. After retraining, alcohol responding was extinguished for 14 days. Subsequently, we tested the effect of muscimol injections into the MRN (0, 12.5, 25, 50 ng) on reinstatement. We also tested the effect of MRN muscimol injections on a measure of reward, conditioned place preference (CPP) and performance in the five-choice serial reaction time task (5-CSRTT), which tests a variety of psychological processes including sustained attention and impulsivity. MRN muscimol injections strongly reinstated alcohol seeking and this effect was not reversed by the depletion of 5-HT with 5,7-DHT. MRN muscimol injections did not induce a CPP, but did significantly impair multiple aspects of performance on the 5-CSRTT, including a marked increase in premature, or impulsive, responding. Together with our previous findings, these results suggest that the inhibition of MRN projection neurons provokes alcohol seeking. Results from the 5-CSRTT suggest that increased impulsivity may contribute to these effects.

Effect of foot shock stress on the interferon-γ production of murine intestinal intraepithelial lymphocytes

To investigate the effect of stress on interferon (IFN)-γ production by intestinal intraepithelial lymphocytes (IEL), we exposed male C3H/HeN mice to electric foot shock for 30 min a day for 5 consecutive days. Immediately after the final foot shock stress, IEL from small intestine were isolated by Percoll density gradient. The stress induced a marked suppression of IFN-γ production by IEL stimulated with immobilized anti-CD3 mAb and a marked decrease in the proportion of IFN-γ-producing CD3 + IEL or αβTCR + IEL stimulated with PMA + ionomycin. The αβTCR + subset was the major cause of stress-induced suppression of IFN-γ production by IEL. Glucocorticoid induced the suppression of IFN-γ production by IEL in vitro, which was reversed by mifepristone (RU486), a glucocorticoid receptor antagonist. In vivo administration of RU486 reversed the stress-induced suppression of IFN-γ production by IEL. In conclusion, repeated foot shock stress suppressed IFN-γ production of IEL by stress-induced elevation of endogenous glucocorticoid. Substantial suppression of the αβTCR + subset was the major cause of the suppression.

Inhibition of stress- or anxiogenic-drug-induced increases in dopamine release in the rat prefrontal cortex by long-term treatment with antidepressant drugs.

The effects of long-term treatment with imipramine or mirtazapine, two antidepressant drugs with different mechanisms of action, on the response of cortical dopaminergic neurons to foot-shock stress or to the anxiogenic drug FG7142 were evaluated in freely moving rats. As expected, foot shock induced a marked increase (+ 90%) in the extracellular concentration of dopamine in the prefrontal cortex of control rats. Chronic treatment with imipramine or mirtazapine inhibited or prevented, respectively, the effect of foot-shock stress on cortical dopamine output. Whereas acute administration of the anxiogenic drug FG7142 induced a significant increase (+ 60%) in cortical dopamine output in control rats, chronic treatment with imipramine or mirtazapine completely inhibited this effect. In contrast, the administration of a single dose of either antidepressant 40 min before foot shock, had no effect on the response of the cortical dopaminergic innervation to stress. These results show that long-term treatment with imipramine or mirtazapine inhibits the neurochemical changes elicited by stress or an anxiogenic drug with an efficacy similar to that of acute treatment with benzodiazepines. Given that episodes of anxiety or depression are often preceded by stressful events, modulation by antidepressants of the dopaminergic response to stress might be related to the anxiolytic and antidepressant effects of these drugs.

Effects of footshock stress on superoxide dismutase and glutathione peroxidase enzyme activities and thiobarbituric acid reactive substances levels in the rat prefrontal cortex and striatum

Mild footshock stress results in an increase dopamine metabolism in the prefrontal cortex. Increases in either the intensity or duration of stress enhance dopamine metabolism in the nucleus accumbens and striatum, as well as in the prefrontal cortex. Dopamine is metabolized by monoamine oxidase with hydrogen peroxide as a product. In this study we have demonstrated that while very mild (0.2 mA) footshock stress did not change glutathione peroxidase activity in the rat prefrontal cortex and striatum, more intense (1.6 mA) footshock stress increased glutathione peroxidase activity at 0, 15, 30 and 60 min after the footshock in the prefrontal cortex and at 30 min after the footshock in the striatum. Stress did not change superoxide dismutase activity and thiobarbituric acid reactive substances levels. These results indicate that increased dopamine metabolism induced by footshock stress is probably responsible for the increase of glutathione peroxidase activity.

Effects of foot-shock stress on morphine analgesia, tolerance and physical dependence in adrenalectomized rats

Effects of foot-shock stress on morphine analgesia, tolerance and physical dependence in adrenalectomized rats

O-65 - Effect of foot-shock stress on light - induced entrainment of circadian wheel-running rhythm in hamsters

O-65 - Effect of foot-shock stress on light - induced entrainment of circadian wheel-running rhythm in hamsters

P-244 - Effect of Footshock stress on the Extracellular γ-aminobutyric Acid Levels in Rat Basolateral Amygdaloid Nucleus

P-244 - Effect of Footshock stress on the Extracellular γ-aminobutyric Acid Levels in Rat Basolateral Amygdaloid Nucleus

Inhibitory effect of foot shock stress on light-induced phase shifts of hamster wheel-running rhythm

Inhibitory effect of foot shock stress on light-induced phase shifts of hamster wheel-running rhythm

2114 Inhibitory effect of foot shock stress on light-induced phase shifts of hamster wheel-running rhythm

2114 Inhibitory effect of foot shock stress on light-induced phase shifts of hamster wheel-running rhythm

Effects of footshock stress on regional brain monoamine metabolism and the acquisition of conditioned freezing in rats previously exposed to repeated methamphetamine

1. 1. Effects of footshock stress on regional brain DA and 5-HT metabolism and the acquisition of conditioned fear in male Wistar-King rats previously exposed to repeated MA were examined. 2. 2. MA-pretreated rats exhibited more freezing than control rats in the conditioned fear test. 3. 3. The HVA levels in the striatum was elevated by footshock only in MA-treated rats but not saline-treated rats. Furthermore, MA-treated rats showed increased metabolism of DA in the mPFC, even when placed in the shock chamber without shocks. 4. 4. The brain serotonergic responsiveness to fear conditioning was also attenuated by repeated administration of MA. 5. 5. These results suggest that not only the brain DA systems but also the brain 5-HT systems play an important role for the development of MA-induced emotional hypersensitivity to stress.

Effects of footshock stress upon spleen and peripheral blood lymphocyte mitogenic responses in rats with lesions of the paraventricular nuclei

To assess the role of the hypothalamic paraventricular nucleus (PVN) in mediating stressor-induced immune alterations, male Lewis rats were subjected to a 1-h session of intermittent footshock stress or home cage conditions 6 days after receiving bilateral or sham PVN lesions. Splenic and peripheral blood lymphocyte proliferative responses to the non-specific mitogens, concanavalin A (ConA) and phytohemagglutinin (PHA), were subsequently measured as were plasma corticosterone levels. In sham-operated rats, footshock markedly elevated plasma corticosterone levels and concurrently suppressed the proliferative responses of peripheral blood and splenic lymphocytes. In PVN-lesioned rats, however, the shock-induced suppression of lymphocyte proliferation in the peripheral blood and the elevation of plasma corticosterone were significantly attenuated, while lymphocyte proliferation in the spleen was suppressed below the level of the sham-treated animals. Thus, by utilizing ablation studies, we have determined that the PVN may play a direct role in the alteration of lymphocyte function during stress, and an intact PVN buffers the effect of stress on the responsiveness of spleen lymphocytes to non-specific mitogens.

Enhanced stress-induced dopamine release in the prefrontal cortex of amphetamine-sensitized rats

This study examined the extent to which chronic d-amphetamine administration sensitizes animals to some behavioral and neurochemical effects of foot shock stress. Rats received daily injections of saline for 14 days or d-amphetamine (2 mg/kg 7 days and 4 mg/kg 7 days). After a 7 day drug abstinent period, extracellular dopamine, 3,4-dihydroxyphenylacetic acid and homovanillic acid concentrations were measured in the medial prefrontal cortex using in vivo microdialysis in freely moving rats. The behavioral responses to mild foot shock stress were enhanced in the d-amphetamine-pretreated subjects. Concomitant with this behavioral sensitization, d-amphetamine-pretreated subjects showed greater stress-induced increases in extracellular dopamine in the medial prefrontal cortex than in controls. d-Amphetamine (2 mg/kg)-induced stereotyped behavior was also enhanced in the amphetamine-pretreated animals compared to controls; however, d-amphetamine-induced increases in extracellular dopamine in the medial prefrontal cortex were not enhanced in the amphetamine-pretreated group. These results suggest that the mesocortical dopaminergic system is involved in cross-sensitization between d-amphetamine and stress, but not in d-amphetamine-induced behavioral sensitization.

Enhancement of Antigen-Specific Humoral and Cell-Mediated Immunity by Electric Footshock Stress in Rats

The effect of footshock stress on the induction phase of sensitization to keyhole limpet hemocyanin (KLH) introduced intraperitoneally was studied in adult male Sprague– Dawley rats. Rats were shocked at Days −1, 0, 1, and 3 relative to sensitization with 50 μg KLH and 14 days later were intradermally injected with 25 μg KLH or were noninjected. Anti-KLH IgG levels were measured in serum by ELISA and were enhanced in stressed versus control rats shocked on Days 0 or 1; splenocyte proliferation to KLH in vitro was also found to be enhanced in shocked rats compared to that in nonshocked rats. Skin at the challenge sites was removed and histologically examined for infiltrate density. There was an increased infiltrate in animals shocked on Days 0 or 1 in comparison to nonshocked controls. The increased humoral and cell-mediated anti-KLH immunity in stressed rats is evidence for enhanced immune function by exposure to footshock proximal to the induction phase of the immune response. The possibility of a generalized increase in immune function in stressed rats is doubtful since splenocyte proliferation to the T-cell mitogens concanavalin A (Con A) and phytohemagglutinin and the B-cell mitogen lipopolysaccharide showed no alteration between control and stressed rats at the time of sacrifice.

The effects of footshock stress on regional brain dopamine metabolism and pituitary β-endorphin release in rats previously sensitized to amphetamine

The repeated intermittent administration of amphetamine (AMP) produces an enduring enhancement in the response of dopamine (DA) systems in the brain to a subsequent “challenge” with amphetamine. However, former amphetamine addicts are not only hypersensitive to amphetamine, but also to “physical or psychologtical stress”. This suggests that sensitization to amphetamine may change the response of DA neurons in brain to subsequent stress. To explore this idea, the effects of footshock stress on regional metabolism of DA in brain, and on the concentrations of plasma β-endorphin and N-acetylated β-endorphin, were studied in rats previously exposed to amphetamine or saline. It was found that: (I) Prior treatment with amphetamine produced enduring (at least 7 days) changes in the dopaminergic response to footshock in the medial frontal cortex, hypothalamus, dorsolateral striatum and nucleus accumbens. Generally, rats pretreated with amphetamine showed a greater initial reduction in concentrations of DA in response to footshock, and a greater elevation in concentrations of metabolites of DA and/or metabolite/transmitter ratios, compared to nonhandled control rats. (2) In some regions of the brain repeated injections of saline produced changes in the response to subsequent footshock that were comparable to those produced by amphetamine. (3) Prior treatment with amphetamine enhanced theelease of β-endorphin and N-acetylated β-endorphin from the pituitary elicited by footshock stress. It is concluded that repeated intermittent treatment with amphetamine or stress (injections of saline) produce enduring changes in the response of DA neurons and the pituitary to subsequent stress. These changes may be responsible for the hypersensitivity to stress reported in former amphetamine addicts, and in rats previously sensitized to amphetamine.

Effects of footshock stress and morphine on natural killer lymphocytes in rats: studies of tolerance and cross-tolerance

Exposure to a form of footshock stress known to cause opioid-mediated analgesia suppresses the cytotoxic activity of natural killer (NK) cells in rats. This suppression is blocked by the opioid antagonist, naltrexone and is mimicked by morphine administration, suggesting mediation by opioid receptors. Supporting this hypothesis, we now report that the morphine-induced suppression of NK activity shows tolerance after 14 daily injections. The NK-suppressive effect of stress, however, shows neither tolerance with repetition nor cross-tolerance in morphine-tolerant rats.

Morphine analgesia: enhancement by shock-associated cues.

Recent research has shown that rats exposed to repeated stress display enhanced morphine analgesia. This study examined the possible contribution of classically conditioned analgesia to this effect. First, drug-naive rats exposed to nine daily sessions of stress, each consisting of a single 45-s exposure to footshock, subsequently displayed enhanced analgesic responsiveness to morphine 1 and 10 days after stress (Experiments 1, 2, and 5). This enhancement was also observed in morphine-experienced rats 1 and 8 days after stress (Experiment 1). Second, the effect of footshock stress on morphine analgesia was found to be specific to the environment in which stress was administered (Experiments 2 and 3). Rats tested in the same distinctive environment in which stress was administered displayed enhanced morphine analgesia; rats shocked elsewhere did not differ from nonshocked controls (Experiment 2). Third, conditioned analgesia was found under the same conditions that yielded enhanced morphine analgesia (Experiments 2 and 4). Lastly, both this conditioned analgesia and the acute analgesia elicited by the footshock stressor were found to be attenuated by naloxone (Experiments 5 and 6). These data are consistent with the hypothesis that the enhanced morphine analgesia observed after repeated footshock stress reflects the contribution of an opioid mediated , conditioned analgesia elicited by cues formerly paired with the stressor.