Abstract:Chronic stress enhances risk for psychiatric disorders, and in animal models is known to evoke depression-like behavior accompanied by perturbed neurohormonal, metabolic, neuroarchitectural and transcriptional changes. Serotonergic neurotransmission, including serotonin2A (5-HT2A) receptors, have been implicated in mediating specific aspects of stress-induced responses. Here we investigated the influence of chronic unpredictable stress (CUS) on depression-like behavior, serum metabolic measures, and gene expre… Show more
“…Interestingly, while we did observe the previously reported baseline anxiolytic behavioral response in 5-HT 2A −/− male and female mice (Supplementary Figure S1) [10,14], the vehicle-treated 5-HT 2A −/− cohorts used for the acute Jund. We also performed qpCR analysis for the Htr2a to further confirm our genotyping results.…”
Section: -Ht 2a Receptor Deficiency and Acute Flx Evoked Anxiety-likcontrasting
confidence: 50%
“…Further, we addressed the degree of neural activation evoked by acute Flx in the paraventricular nucleus (PVN) of the hypothalamus and the prefrontal cortex (PFC) in 5-HT 2A −/− and WT mice, and gene expression of several activity-regulated, immediate early genes (IEGs) in the PFC. 5-HT 2A −/− mice have been previously reported to exhibit a baseline anxiolytic phenotype [10,14], higher firing rates of dorsal raphe 5-hydroxytryptamine or serotonin (5-HT) neurones [15] and also to display treatment resistance to chronic Flx administration [16]. Our results reveal that the anxiogenic effects of acute Flx treatment, as well as the enhanced serum corticosterone levels are unaltered in 5-HT 2A −/− mice of both sexes.…”
Section: Introductionmentioning
confidence: 52%
“…Serotonin 2A receptor (5-HT 2A ) knockout mice (5-HT 2A −/− ) [10] and wild-type (WT) littermate controls of both sexes (4-7 months) were maintained on a 129S6/SvEv background, and group housed on a 12-h normal light-dark cycle, with access to food and water ad libitum in the Tata Institute of Fundamental Research (TIFR) animal house facility. Genotypes were confirmed using PCR analysis as described previously [14]. All experimental procedures followed the guidelines of the Committee for Supervision and Care of Experimental Animals (CPCSEA), Government of India, and were approved by the TIFR Institutional Animal Ethics committee in accordance with the National Institutes of Health guide for the care and use of Laboratory animals (NIH Publication No.…”
Section: Animals and Drug Treatmentmentioning
confidence: 99%
“…Animals were assessed for anxiety-like response on the OFT as described previously [14]. Briefly, mice were placed in one corner of the arena and allowed to explore the arena for 10 min under dim light conditions.…”
Section: Oft and Epmmentioning
confidence: 99%
“…−/− mice exhibit acute Flx-induced enhanced anxiety-like behavior in the OFT 5-HT 2A receptor knockout (5-HT 2A −/− ) mice have been reported to exhibit reduced anxiety-like behavior across both sexes (Supplementary Figure S1) [10,14]. Acute Flx treatment is known to enhance anxiety-like behavioral responses [3].…”
Background: Acute treatment with the selective serotonin reuptake inhibitor (SSRI), fluoxetine (Flx), induces anxiety-like behavioral effects. The serotonin2A receptor (5-HT2A) is implicated in the modulation of anxiety-like behavior, however its contribution to the anxiogenic effects of acute Flx remains unclear. Here, we examined the role of the 5-HT2A receptor in the effects of acute Flx on anxiety-like behavior, serum corticosterone levels, neural activation and immediate early gene (IEG) expression in stress-responsive brain regions, using 5-HT2A receptor knockout (5-HT2A−/−) mice of both sexes. Methods: 5-HT2A−/− and wild-type (WT) male and female mice received a single administration of Flx or vehicle, and were examined for anxiety-like behavior, serum corticosterone levels, FBJ murine osteosarcoma viral oncogene homolog peptide (c-Fos) positive cell numbers in stress-responsive brain regions of the hypothalamus and prefrontal cortex (PFC), and PFC IEG expression. Results: The increased anxiety-like behavior and enhanced corticosterone levels evoked by acute Flx were unaltered in 5-HT2A−/− mice of both sexes. 5-HT2A−/− female mice exhibited a diminished neural activation in the hypothalamus in response to acute Flx. Further, 5-HT2A−/− male, but not female, mice displayed altered baseline expression of several IEGs (brain-derived neurotrophic factor (Bdnf), Egr2, Egr4, FBJ osteosarcoma gene (Fos), FBJ murine osteosarcoma viral oncogene homolog B (Fosb), Fos-like antigen 2 (Fosl2), Homer scaffolding protein (Homer) 1-3 (Homer1-3), Jun proto-oncogene (Jun)) in the PFC. Conclusion: Our results indicate that the increased anxiety and serum corticosterone levels evoked by acute Flx are not influenced by 5-HT2A receptor deficiency. However, the loss of function of the 5-HT2A receptor alters the degree of neural activation of the paraventricular nucleus (PVN) of the hypothalamus in response to acute Flx, and baseline expression of several IEGs in the PFC in a sexually dimorphic manner.
“…Interestingly, while we did observe the previously reported baseline anxiolytic behavioral response in 5-HT 2A −/− male and female mice (Supplementary Figure S1) [10,14], the vehicle-treated 5-HT 2A −/− cohorts used for the acute Jund. We also performed qpCR analysis for the Htr2a to further confirm our genotyping results.…”
Section: -Ht 2a Receptor Deficiency and Acute Flx Evoked Anxiety-likcontrasting
confidence: 50%
“…Further, we addressed the degree of neural activation evoked by acute Flx in the paraventricular nucleus (PVN) of the hypothalamus and the prefrontal cortex (PFC) in 5-HT 2A −/− and WT mice, and gene expression of several activity-regulated, immediate early genes (IEGs) in the PFC. 5-HT 2A −/− mice have been previously reported to exhibit a baseline anxiolytic phenotype [10,14], higher firing rates of dorsal raphe 5-hydroxytryptamine or serotonin (5-HT) neurones [15] and also to display treatment resistance to chronic Flx administration [16]. Our results reveal that the anxiogenic effects of acute Flx treatment, as well as the enhanced serum corticosterone levels are unaltered in 5-HT 2A −/− mice of both sexes.…”
Section: Introductionmentioning
confidence: 52%
“…Serotonin 2A receptor (5-HT 2A ) knockout mice (5-HT 2A −/− ) [10] and wild-type (WT) littermate controls of both sexes (4-7 months) were maintained on a 129S6/SvEv background, and group housed on a 12-h normal light-dark cycle, with access to food and water ad libitum in the Tata Institute of Fundamental Research (TIFR) animal house facility. Genotypes were confirmed using PCR analysis as described previously [14]. All experimental procedures followed the guidelines of the Committee for Supervision and Care of Experimental Animals (CPCSEA), Government of India, and were approved by the TIFR Institutional Animal Ethics committee in accordance with the National Institutes of Health guide for the care and use of Laboratory animals (NIH Publication No.…”
Section: Animals and Drug Treatmentmentioning
confidence: 99%
“…Animals were assessed for anxiety-like response on the OFT as described previously [14]. Briefly, mice were placed in one corner of the arena and allowed to explore the arena for 10 min under dim light conditions.…”
Section: Oft and Epmmentioning
confidence: 99%
“…−/− mice exhibit acute Flx-induced enhanced anxiety-like behavior in the OFT 5-HT 2A receptor knockout (5-HT 2A −/− ) mice have been reported to exhibit reduced anxiety-like behavior across both sexes (Supplementary Figure S1) [10,14]. Acute Flx treatment is known to enhance anxiety-like behavioral responses [3].…”
Background: Acute treatment with the selective serotonin reuptake inhibitor (SSRI), fluoxetine (Flx), induces anxiety-like behavioral effects. The serotonin2A receptor (5-HT2A) is implicated in the modulation of anxiety-like behavior, however its contribution to the anxiogenic effects of acute Flx remains unclear. Here, we examined the role of the 5-HT2A receptor in the effects of acute Flx on anxiety-like behavior, serum corticosterone levels, neural activation and immediate early gene (IEG) expression in stress-responsive brain regions, using 5-HT2A receptor knockout (5-HT2A−/−) mice of both sexes. Methods: 5-HT2A−/− and wild-type (WT) male and female mice received a single administration of Flx or vehicle, and were examined for anxiety-like behavior, serum corticosterone levels, FBJ murine osteosarcoma viral oncogene homolog peptide (c-Fos) positive cell numbers in stress-responsive brain regions of the hypothalamus and prefrontal cortex (PFC), and PFC IEG expression. Results: The increased anxiety-like behavior and enhanced corticosterone levels evoked by acute Flx were unaltered in 5-HT2A−/− mice of both sexes. 5-HT2A−/− female mice exhibited a diminished neural activation in the hypothalamus in response to acute Flx. Further, 5-HT2A−/− male, but not female, mice displayed altered baseline expression of several IEGs (brain-derived neurotrophic factor (Bdnf), Egr2, Egr4, FBJ osteosarcoma gene (Fos), FBJ murine osteosarcoma viral oncogene homolog B (Fosb), Fos-like antigen 2 (Fosl2), Homer scaffolding protein (Homer) 1-3 (Homer1-3), Jun proto-oncogene (Jun)) in the PFC. Conclusion: Our results indicate that the increased anxiety and serum corticosterone levels evoked by acute Flx are not influenced by 5-HT2A receptor deficiency. However, the loss of function of the 5-HT2A receptor alters the degree of neural activation of the paraventricular nucleus (PVN) of the hypothalamus in response to acute Flx, and baseline expression of several IEGs in the PFC in a sexually dimorphic manner.
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