scholarly journals Yokukansan Increases 5-HT1AReceptors in the Prefrontal Cortex and Enhances 5-HT1AReceptor Agonist-Induced Behavioral Responses in Socially Isolated Mice

2015 ◽  
Vol 2015 ◽  
pp. 1-9 ◽  
Author(s):  
Toshiyuki Ueki ◽  
Kazushige Mizoguchi ◽  
Takuji Yamaguchi ◽  
Akinori Nishi ◽  
Yasushi Ikarashi ◽  
...  

The traditional Japanese medicine yokukansan has an anxiolytic effect, which occurs after repeated administration. In this study, to investigate the underlying mechanisms, we examined the effects of repeated yokukansan administration on serotonin 1A (5-HT1A) receptor density and affinity and its expression at both mRNA and protein levels in the prefrontal cortex (PFC) of socially isolated mice. Moreover, we examined the effects of yokukansan on a 5-HT1Areceptor-mediated behavioral response. Male mice were subjected to social isolation stress for 6 weeks and simultaneously treated with yokukansan. Thereafter, the density and affinity of 5-HT1Areceptors were analyzed by a receptor-binding assay. Levels of 5-HT1Areceptor protein and mRNA were also measured. Furthermore, (±)-8-hydroxy-2-(dipropylamino)tetralin hydrobromide (8-OH-DPAT; a 5-HT1Areceptor agonist) was injected intraperitoneally, and rearing behavior was examined. Social isolation stress alone did not affect 5-HT1Areceptor density or affinity. However, yokukansan significantly increased receptor density and decreased affinity concomitant with unchanged protein and mRNA levels. Yokukansan also enhanced the 8-OH-DPAT-induced decrease in rearing behavior. These results suggest that yokukansan increases 5-HT1Areceptors in the PFC of socially isolated mice and enhances their function, which might underlie its anxiolytic effects.

2016 ◽  
Vol 2016 ◽  
pp. 1-13 ◽  
Author(s):  
Alessandro Ieraci ◽  
Alessandra Mallei ◽  
Maurizio Popoli

Stress is a major risk factor in the onset of several neuropsychiatric disorders including anxiety and depression. Although several studies have shown that social isolation stress during postweaning period induces behavioral and brain molecular changes, the effects of social isolation on behavior during adulthood have been less characterized. Aim of this work was to investigate the relationship between the behavioral alterations and brain molecular changes induced by chronic social isolation stress in adult male mice. Plasma corticosterone levels and adrenal glands weight were also analyzed. Socially isolated (SI) mice showed higher locomotor activity, spent less time in the open field center, and displayed higher immobility time in the tail suspension test compared to group-housed (GH) mice. SI mice exhibited reduced plasma corticosterone levels and reduced difference between right and left adrenal glands. SI showed lower mRNA levels of the BDNF-7 splice variant, c-Fos, Arc, and Egr-1 in both hippocampus and prefrontal cortex compared to GH mice. Finally, SI mice exhibited selectively reduced mGluR1 and mGluR2 levels in the prefrontal cortex. Altogether, these results suggest that anxious- and depressive-like behavior induced by social isolation stress correlates with reduction of several neuroplasticity-related genes in the hippocampus and prefrontal cortex of adult male mice.


2021 ◽  
Vol 22 (19) ◽  
pp. 10678
Author(s):  
Francesco Matrisciano ◽  
Graziano Pinna

Social behavioral changes, including social isolation or loneliness, increase the risk for stress-related disorders, such as major depressive disorder, posttraumatic stress disorder (PTSD), and suicide, which share a strong neuroinflammatory etiopathogenetic component. The peroxisome-proliferator activated receptor (PPAR)-α, a newly discovered target involved in emotional behavior regulation, is a ligand-activated nuclear receptor and a transcription factor that, following stimulation by endogenous or synthetic ligands, may induce neuroprotective effects by modulating neuroinflammation, and improve anxiety and depression-like behaviors by enhancing neurosteroid biosynthesis. How stress affects epigenetic mechanisms with downstream effects on inflammation and emotional behavior remains poorly understood. We studied the effects of 4-week social isolation, using a mouse model of PTSD/suicide-like behavior, on hippocampal PPAR-α epigenetic modification. Decreased PPAR-α expression in the hippocampus of socially isolated mice was associated with increased levels of methylated cytosines of PPAR-α gene CpG-rich fragments and deficient neurosteroid biosynthesis. This effect was associated with increased histone deacetylases (HDAC)1, methyl-cytosine binding protein (MeCP)2 and decreased ten-eleven translocator (TET)2 expression, which favor hypermethylation. These alterations were associated with increased TLR-4 and pro-inflammatory markers (e.g., TNF-α,), mediated by NF-κB signaling in the hippocampus of aggressive mice. This study contributes the first evidence of stress-induced brain PPAR-α epigenetic regulation. Social isolation stress may constitute a risk factor for inflammatory-based psychiatric disorders associated with neurosteroid deficits, and targeting epigenetic marks linked to PPAR-α downregulation may offer a valid therapeutic approach.


2014 ◽  
Vol 393 (1-2) ◽  
pp. 43-57 ◽  
Author(s):  
Jelena Zlatković ◽  
Nevena Todorović ◽  
Maja Bošković ◽  
Snežana B. Pajović ◽  
Miroslav Demajo ◽  
...  

eNeuro ◽  
2017 ◽  
Vol 4 (2) ◽  
pp. ENEURO.0034-17.2017 ◽  
Author(s):  
Esther Castillo-Gómez ◽  
Marta Pérez-Rando ◽  
María Bellés ◽  
Javier Gilabert-Juan ◽  
José Vicente Llorens ◽  
...  

2001 ◽  
Vol 281 (1) ◽  
pp. R352-R358 ◽  
Author(s):  
Olga V. Fedorova ◽  
David E. Anderson ◽  
Edward G. Lakatta ◽  
Alexei Y. Bagrov

Our study investigated the hypothesis that the combination of a high NaCl diet and social isolation stress would increase systolic blood pressure (SBP) and endogenous sodium pump ligands (SPL), ouabainlike compound (OLC), and marinobufagenin (MBG). Excretion of MBG and OLC, SBP, and organ weights were studied in four groups ( n = 8) of male Fisher 344 × Norwegian brown rats: controls, socially isolated (Iso), 4% NaCl diet (Salt), and the combination of Salt and Iso (Iso+Salt). In Salt, MBG excretion increased by 78% ( P < 0.01), whereas SBP and OLC remained unchanged. In Iso, SBP and MBG did not change, but OLC peaked on day 1. In the Iso+Salt, SBP increased by 9 mmHg, MBG excretion increased (42.0 ± 7.6 vs. 10.0 ± 1.5 pmol/24 h, P < 0.01), whereas OLC peaked at day 1(25.0 ± 2.5 vs. 10.0 ± 2.0 pmol/24 h, P < 0.01) and remained elevated. Heart and kidney weights were increased in Salt and Iso+Salt. Aortic weights were increased in Iso and Iso+Salt. Thus a high NaCl intake stimulates MBG excretion, whereas isolation stress stimulates OLC. The combination of Salt and Iso is accompanied by marked stimulation of both SPL.


2017 ◽  
Vol 15 (4) ◽  
pp. 38-45
Author(s):  
Petr D Shabanov ◽  
Petr M Vinogradov ◽  
Andrei A Lebedev ◽  
Roman O Roik ◽  
Vitalii I Morozov

Wistar rats were rearing in conditions of social isolation from others beginning with 20th day of life till adulthood (90-100 days). In adult rats, a conditioned place preference (CPP) of ethanol (0.5 g/kg ip) was trained, and behavior in open field, elevated plus maze and intruder-resident test was examined. Intranasal administration of [D-Lys3]-GHRP-6, a peptide ghrelin antagonist (10 µg in 20 µl), to isolated rats blocked formation and expression (recovery) of CPP of ethanol that supported participation of ghrelin system in regulation of positive reinforcement activated by ethanol. Intranasal administration of ghrelin (20 µg in 20 µl) to rats reared in conditions of social isolation produced a typical anxiogenic effect, elevated exploratory activity, aggression signs and reduction of communicative behavior. In rats reared in conditions of social isolation, [D-Lys3]-GHRP-6, a ghrelin antagonist, possessed anxiolytic effect, reduced explorative activity, communicative behavior and aggression. It is concluded that ghrelin system of the brain participates in control of emotional, explorative behavior and motor activity in rats rearing in conditions of social isolation stress. (For citation: Shabanov PD, Vinogradov PM, Lebedev AA, et al. Ghrelin system of the brain participates in control of emotional, explorative behavior and motor activity in rats rearing in conditions of social isolation stress. Reviews on Clinical Pharmacology and Drug Therapy. 2017;15(4):38-45. doi: 10.17816/RCF15438-45).


2009 ◽  
Vol 136 (5) ◽  
pp. A-556
Author(s):  
Hiroshi Takeda ◽  
Shuichi Muto ◽  
Takehiko Katsurada ◽  
Yayoi Inagaki ◽  
Kazuaki Tsuchiya ◽  
...  

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