Restraint stress

Chronic corticosterone treatment or repeated restraint stress promotes atrophy of apical dendrites of CA3 pyramidal neurons. 

The stress-associated shift in Thl/Th2 cytokines observed in human subjects has also been demonstrated in restraint-stressed mice. Associated with the shift towards a Th2 response are a significant decrease in NK cell activity, decreased IFN-y production by Con A-stimulated splenocytes, and a concomitant increase in serum corticosterone levels after 24 hours of restraint.30 These observations are consistent with studies on the effects of restraint stress and the immune response to viral infection. Restraint-stressed mice exhibited a decline in NK cell activity and a decrease in the generation of virus-specific cytotoxic T lymphocytes to HSV-l after primary infection, which resulted in an increase in the replication of the virus at the site of infection.3132... 

Consistent with this hypothesis are data from a study with mice. Social disruption of groups of 5 male BALB/c mice was shown to increase aggression among cohorts, activate the HPA axis, and reactivate latent HS V-1 in more than 40% of latently infected mice.46 In contrast, restraint stress, which can down-regulate the innate and HSV-1 specific immune response, did not reactivate latent HSV-1.47 HPA activation, as measured by serum corticosterone levels, was comparable using both types of stressors. 

The hypothesis that stress can modulate MMP expression is also supported by studies in mice. Using social isolation as a stressor, the mRNA levels of MMP-2, MMP-9, matrix-type matrix metalloproteinase-1 (MT1-MMP), and urokinase-type plasminogen activator were higher in the tumor and liver tissues of the isolated mice than in control mice.91 Furthermore, a recent study has shown that restraint stress causes an increase in expression of the plasminogen activator inhibitor-1, another key player in the plas-minogen/plasmin enzyme system in mice.92 As these enzymes have been described to have functions besides their role in ECM remodeling,93 studies on stress-related effects on MMP/TIMP balance have implications in the relationship between stress and cancer initiation and progression.. 

Iwakabe, K. et al., The restraint stress drives a shift in Thl/Th2 balance toward Th2-domi-nant immunity in mice, Immunol. Lett., 62, 39, 1998. 

Sheridan, I.F. et al.., Restraint stress differentially affects anti-viral cellular and humoral immune responses in mice, J. Neuroimmunol., 31, 245, 1991. 

Hunzeker, J. et al., Modulation of natural killer cell activity by restraint stress during an influenza A/PR8 infection in mice, Brain Behav. Immun., 18, 526, 2004. 

Campbell, T. et al., The effects of restraint stress on the neuropathogenesis of Theiler s virus infection I. Acute disease, Brain Behav. Immun, 15, 235, 2001. 

Gammie, S.C. and Stevenson, S.A. (2006) Effect of daily and acute restraint stress during lactation on maternal aggression and behavior in mice. Stress. 9, 171-180. 

Merlo Pich E, Lorang M, Yeganeh M, Rodriguez de Eonseca E, Raber J, et al. 1995. Increase of extracellular corticotropinreleasing factor-like immunoreactivity levels in the amygdala of awake rats during restraint stress and ethanol withdrawal as measured by microdialysis. J Neurosci 15(8) 5439-5447. 

Stress results in alterations in behavior and physiology that can be either adaptive or maladaptive. Although mice deficient in the calcium-stimulated adenylyl cyclase type VIII (ACS) exhibit indices of anxiety comparable with that of wildtype mice at baseline, ACS KO mice do not show normal increases in behavioral features of anxiety when subjected to repeated stress such as repetitive or post-restraint stress testing in the elevated plus maze test (Schaefer et al. 2000). Although these findings suggest a role for ACS in the modulation of anxiety, the mechanism by which ACS deficiency results in impaired stress-... 

Farisse J, Boulenguez P, Semont A, Hery F, Barden N, Faudon M, Hery M (1999) Regional serotonin metabolism imder basal and restraint stress conditions in the brain of transgenic mice with impaired glucocorticoid receptor fimction. Neuroendocrinology 70 413-421... 

Lee YE, Byun SK, Shin S et al (2008) Effect of maternal restraint stress on fetal development of ICRmice. Exp Anim 57 19-25... 

Antiulcerogenic activity. Colloidal solution, administered orally to rats at a dose of 50 mg/kg, 60 minutes before experiment, produced significant protection against gastric ulcers induced by 2 hours cold restraint stress, aspirin, and 4 hours pylorus ligation " . ... 

Sanchez, M.M., Aguado, R, Sanchez-Toscano, F., and Saphier, D. (1998) Neuroendocrine and immunocytochemical demonstrations of decreased hypothalamo-pituitary-adrenal axis responsiveness to restraint stress after long-term social isolation. Endocrinology 139 579-587. 

Kurata, ., Y. Tanii, R. Shibata, and M. Kurachi. 1993. "Differential Effects of Tight and Loose 2-hour Restraint Stress on Extracellular Concentrations of Dopamine in Nucleus Accumbens and Anteromedial Frontal Cortex." Japanese Journal of Psychiatry and Neurology 47 57-61. 

Ghoshal K, Wang Y, Sheridan JF, Jacob ST (1998) Metallothionein induction in response to restraint stress. Transcriptional control, adaptation to stress, and role of glucocorticoid. J Biol Chem 273 27904-27910... 

Similar to the effect on restraint stress, RmHA (10 mg/kg x 2 ip) inhibited the ACTH and P-END response to insulin-induced hypoglycemia, which increases neuronal HA turnover [30-31]. This inhibitory effect was completely or partly reversed by THIOP. Likewise, the responses of the POMC-derived peptides and corticosterone to immune stimulation with the E.coli lipopolysaccharide (LPS) endotoxin, which augmented neuronal HA turnover, were reduced by RmHA pretreatment [39]. The effect of RmHA was equal to that of HA synthesis inhibition by a-FMH [39]. In lactating female rats suckling-induced ACTH secretion was reduced by pretreatment with RmHA (Fig. 6) as well as by a-FMH [32],... 

The inhibitory efficiency of the H3 receptor agonists varies with the particular form of stress applied, although some of this is likely to be explained by the magnitude of the hormone response induced by the stressor. Thus, the agonists inhibited the ACTH response to hypoglycemia about 75% but only reduced the response to restraint stress by 50%. In accordance with these results... 

Figure 1. Effect of the H3 receptor agonists R(a)methylHA (RHA 10 mg/kg), BP 2-94 (BP 25 mg/kg) or imetit (Imt 2 mg/kg) administered ip at -180 and -60 minutes in combination with saline (Sa) or the H3 receptor antagonist thioperamide (Th 5 mg/kg ip at -180 min) on the ACTH response to restraint stress (5 minutes), insulin-induced hypoglycemia (3 IU/kg ip -45 minutes) or LPS endotoxin (10 pg/kg ip at -120 minutes). The rats were decapitated at 0 minutes. p<0.01 vs. saline control or p<0.05 or p<0.01 vs. stimulus alone and H or nn p<0.05 or p<0.01 vs. stimulus and H3 receptor agonist.

Figure 2. Effect of the H3 receptor agonists R(a)methylHA (RHA) or BP 2-94 (BP) administered in combination with saline (Sa) or the H3 receptor antagonist thioperamide (Th) on the P-END response to restraint stress or insulin-induced hypoglycemia. Further informations are given in legend to figure 1.

In recent experiments we investigated the effect of different H3 receptor agonists on basal or restraint stress-stimulated PRL secretion [Knigge et al. (unpublished observations)]. The H3 receptor compounds RmHA, BP 2-94 or imetit were administered alone or in combination with THIOP before exposure of male rats to restraint stress (Fig. 4). The study design was performed as described above. Five minutes of restraint stress caused a more than 10-fold increase in plasma PRL level. The effect of stress was inhibited by 50 to 80% by RmHA, BP 2-94 or imetit. Concomitant administration of THIOP prevented the inhibitory effect of the H3 receptor agonists. 

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