scholarly journals Role of CRF receptor 1 antagonism in the bed nucleus of the stria terminalis of male rats after intermittent social defeat stress

2019 ◽  
Author(s):  
Mailton Vasconcelos ◽  
Dirson J. Stein ◽  
Matheus Gallas-Lopes ◽  
Luane Landau ◽  
Luiza Behrens ◽  
...  

AbstractWe recently demonstrated that the experience of brief episodes of social defeat caused impairments in social behaviors. Moreover, we provided evidence that the antagonism of corticotropin-releasing factor binding protein (CRFBP) in the bed nucleus of the stria terminalis (BNST) restored social approach in stressed animals. This study aimed to test the relation between corticotropin-releasing factor receptor type 1 (CRFR1) located in the BNST and the establishment of social stress-disrupted behaviors in rats submitted to social defeat in the resident-intruder paradigm. Animals were tested for sweet solution preference, subjected to the elevated-plus maze (EPM), and to the social interaction three-chamber test. Social behavior was tested after BNST drug infusions. The drug used in this study was a CRF receptor 1 antagonist, CP376395 (CP), administered in two doses: 50 ng/0.20 μL/side, and 500 ng/0.20 μL/side. Saline solution was used as vehicle and administered 0.20 μL/side. Socially stressed animals (n = 11) did not differ compared to control animals (n = 11) in the EPM. Stressed animals displayed impaired social behavior, represented by a decrease in time spent in the interaction zone. The lower dose (CP 50 ng/0.20 μL/side) administered intra-BNST restored social behaviors in stressed animals. On the other hand, the higher dose of the CRFR1 antagonist (CP 500 ng/0.20 μL/side) induced social avoidance in rats without a history of agonistic confrontations. These findings implicate BNST CRFR1 signaling in the modulation of social behaviors in rats given the choice to explore an unfamiliar conspecific.

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Midori Nagai ◽  
Hirotaka Nagai ◽  
Chisato Numa ◽  
Tomoyuki Furuyashiki

AbstractSevere environmental and social stress induces dysregulation of sleep along with mood and cognitive disturbances. However, the role and mechanism of this sleep dysregulation remain elusive. Here we evaluated sleep-like inactivity measured by voluntary movements and its relationship to social behaviors in mice without or with social defeat stress as well as the stressed mice with subsequent sleep deprivation. Social defeat stress immediately induced sleep-like inactivity with decreased body temperature. In the social interaction test, the control mice showed high social interest and its correlation with social sniffing intensity, the latter of which indicates positive valence of social sniffing. After the stress, these social characteristics were maintained in stress-resilient mice, but disrupted in stress-susceptible mice, leading to social avoidance. Sleep deprivation after the stress decreased social sniffing intensity along with reduced social interest, but enhanced the exploratory activity with the positive valence of social sniffing. We also found by c-Fos immunohistochemistry that the stress activated sleep-related brain regions, the dorsomedial hypothalamus and ventrolateral periaqueductal gray. Collectively, these findings show that stress activates sleep-related brain regions and induces sleep-like inactivity, contributing to multiple roles of stress-induced sleep for social behaviors.


2019 ◽  
Vol 357-358 ◽  
pp. 104-110 ◽  
Author(s):  
Mailton Vasconcelos ◽  
Dirson J. Stein ◽  
Lucas Albrechet-Souza ◽  
Klaus A. Miczek ◽  
Rosa Maria M. de Almeida

Endocrinology ◽  
2014 ◽  
Vol 156 (2) ◽  
pp. 523-533 ◽  
Author(s):  
Christophe Lenglos ◽  
Juliane Calvez ◽  
Elena Timofeeva

This study compared the effects of relaxin-3 (RLN3) on food intake, plasma corticosterone, and the expression of corticotropin-releasing factor (CRF) in male and female rats. RLN3 was injected into the lateral ventricle at 25, 200, and 800 pmol concentrations. RLN3 at 25 pmol increased food intake (grams) at 30 and 60 minutes after injection in female but not male rats. Female rats also showed higher increase in relative to body weight (BW) food intake (mg/g BW) for all RLN3 concentrations at 30 minutes and for 800 pmol of RLN3 at 60 minutes. Moreover, RLN3 at 800 pmol significantly increased 24-hour BW gain in female but not male rats. At 60 minutes after administration, 800 pmol of RLN3 produced a significant increase in plasma corticosterone and in the expression of CRF and c-fos mRNAs in the parvocellular paraventricular hypothalamic nucleus (PVN) in male but not female rats. The levels of c-fos mRNA in the magnocellular PVN were increased by RLN3 but did not differ between the sexes. Conversely, expression of CRF mRNA in the medial preoptic area was increased in female rats but was not sensitive to 800 pmol of RLN3. In the bed nucleus of the stria terminalis, 800 pmol of RLN3 significantly increased CRF mRNA expression in female but not male rats. Therefore, female rats showed more sensitivity and stronger food intake increase in response to RLN3. The differential effects of RLN3 on CRF expression in the PVN and bed nucleus of the stria terminalis may contribute to the sex-specific difference in the behavioral response.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Katherine A. Partrick ◽  
Anna M. Rosenhauer ◽  
Jérémie Auger ◽  
Amanda R. Arnold ◽  
Nicole M. Ronczkowski ◽  
...  

AbstractSocial stress exacerbates anxious and depressive behaviors in humans. Similarly, anxiety- and depressive-like behaviors are triggered by social stress in a variety of non-human animals. Here, we tested whether oral administration of the putative anxiolytic probiotic strains Lactobacillus helveticus R0052 and Bifidobacterium longum R0175 reduces the striking increase in anxiety-like behavior and changes in gut microbiota observed following social defeat stress in Syrian hamsters. We administered the probiotic at two different doses for 21 days, and 16S rRNA gene amplicon sequencing revealed a shift in microbial structure following probiotic administration at both doses, independently of stress. Probiotic administration at either dose increased anti-inflammatory cytokines IL-4, IL-5, and IL-10 compared to placebo. Surprisingly, probiotic administration at the low dose, equivalent to the one used in humans, significantly increased social avoidance and decreased social interaction. This behavioral change was associated with a reduction in microbial richness in this group. Together, these results demonstrate that probiotic administration alters gut microbial composition and may promote an anti-inflammatory profile but that these changes may not promote reductions in behavioral responses to social stress.


2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Kerstin Camile Creutzberg ◽  
Érika Kestering-Ferreira ◽  
Thiago Wendt Viola ◽  
Luis Eduardo Wearick-Silva ◽  
Rodrigo Orso ◽  
...  

AbstractThe peripartum period is accompanied by numerous physiological and behavioural adaptations organised by the maternal brain. These changes are essential for adequate expression of maternal behaviour, thereby ensuring proper development of the offspring. The corticotropin-releasing factor (CRF) plays a key role in a variety of behaviours accompanying stress, anxiety, and depression. There is also evidence that CRF contributes to maladaptations during the peripartum period. We investigated the effects of CRF in the bed nucleus of the stria terminalis (BNST) of lactating mice during maternal care and analysed locomotor activity and anxiety-like behaviour in the offspring. The BNST has been implicated in anxiety behaviour and regulation of the stress response. The effects of intra-BNST CRF administration were compared with those induced by the limited bedding (LB) procedure, a model that produces altered maternal behaviour. BALB/cJ dams were exposed to five infusions of CRF or saline into the BNST in the first weeks after birth while the LB dams were exposed to limited nesting material from postnatal days (P) 2–9. Maternal behaviour was recorded in intercalated days, from P1-9. Offspring anxiety-like behaviour was assessed during adulthood using the open-field, elevated plus-maze, and light/dark tests. Both intra-BNST CRF and LB exposure produced altered maternal care, represented by decreased arched-back nursing and increased frequency of exits from the nest. These changes in maternal care resulted in robust sex-based differences in the offspring’s behavioural responses during adulthood. Females raised by CRF-infused dams exhibited increased anxiety-like behaviour, whereas males presented a significant decrease in anxiety. On the other hand, both males and females raised by dams exposed to LB showed higher locomotor activity. Our study demonstrates that maternal care is impaired by intra-BNST CRF administrations, and these maladaptations are similar to exposure to adverse early environments. These procedures, however, produce distinct phenotypes in mice during young adulthood and suggest sex-based differences in the susceptibility to poor maternal care.


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