Perinatal paroxetine exposure in Selcetively-bred Low Responder rats
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PROVIDER: PRJNA436721 | ENA |
REPOSITORIES: ENA
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Project description:Selective serotonin reuptake inhibitor (SSRI) antidepressants are the mainstay treatment for the 10-20% of pregnant and postpartum women who suffer major depression, but the effects of SSRIs on their children’s developing brain and later emotional health are poorly understood. SSRI use during pregnancy can elicit antidepressant withdrawal in newborns and increase toddlers’ anxiety and social avoidance. In rodents, perinatal SSRI exposure increases adult depression- and anxiety-like behavior, although certain individuals are more vulnerable to these effects than others. Our study establishes a rodent model of individual differences in susceptibility to perinatal SSRI exposure, utilizing selectively-bred Low Responder (LR) and High Responder (HR) rats that were previously bred for high versus low behavioral response to novelty. Pregnant HR/LR females were chronically treated with the SSRI paroxetine (10 mg/kg/day p.o.) to examine its effects on offspring’s emotional behavior and gene expression in the developing brain. Paroxetine treatment had minimal effect on HR/LR dams’ pregnancy outcomes or maternal behavior. We found that LR offspring, naturally prone to an inhibited/anxious temperament, were susceptible to behavioral abnormalities associated with perinatal SSRI exposure (which exacerbated their Forced Swim Test immobility), while high risk-taking HR offspring were resistant. Microarray studies revealed robust perinatal SSRI-induced gene expression changes in the developing LR hippocampus and amygdala (postnatal days 7-21), including transcripts involved in neurogenesis, synaptic vesicle components, and energy metabolism. These results highlight the LR/HR model as a useful tool to explore the neurobiology of individual differences in susceptibility to perinatal SSRI exposure.
2018-03-03 | GSE111362 | GEO
Project description:Hippocampal Gene Expression in bred High Responder (bHR) vs. bred Low Responder (bLR) Rats
| PRJNA590224 | ENA
Project description:The strong pattern of comorbidity amongst psychiatric disorders is believed to be generated by a spectrum of latent liability, arising from a complex interplay of genetic risk and environmental factors, such as stress and childhood adversity. At one end of this spectrum are internalizing disorders, which are associated with neuroticism, anxiety, and depression. At the other end of the spectrum are externalizing disorders, which are associated with risk-taking and novelty-seeking, as seen in mania, substance abuse, and impulse-control disorders. We model the genetic contributions underlying both extremes of this spectrum by selectively breeding rats that react differently to a novel environment. “Bred high responder” (bHR) rats are highly exploratory with a disinhibited, novelty-seeking temperament, including hyperactivity, aggression, and drug-seeking. “Bred low responder” (bLR) rats are highly-inhibited, exhibiting reduced locomotor activity and anxious and depressive-like behavior. These behavioral propensities are robust and stable, beginning early in development similar to temperament in humans. This RNA-sequencing study examined gene expression in the hippocampus, a region critical for emotional regulation, in generation F37 adult male bHR rats and bLR rats (n=6/group), as well as in rats that showed an intermediate locomotor response to a novel field (“bred Intermediate Responder” or bIR rats, n=6), which were obtained by cross-breeding F37 bHR and bLR rats. Prior to sacrifice, the animals experienced behavioral testing. Locomotor response to a novel environment was assessed between age P50–75 as part of our selective breeding paradigm. We also measured anxiety-like behavior in adulthood (bHR/bLR: P160-P167; bIR: P65-75) using the percent time spent in the open arms of an Elevated Plus Maze (EPM; 5 min test). These behavioral testing results are provided here along with the gene expression data.
2020-06-02 | GSE140598 | GEO
Project description:The strong pattern of comorbidity amongst psychiatric disorders is believed to be generated by a spectrum of latent liability, arising from a complex interplay of genetic risk and environmental factors, such as stress and childhood adversity. At one end of this spectrum are internalizing disorders, which are associated with neuroticism, anxiety, and depression. At the other end of the spectrum are externalizing disorders, which are associated with risk-taking and novelty-seeking, as seen in mania, substance abuse, and impulse-control disorders. We model the genetic contributions underlying both extremes of this spectrum by selectively breeding rats that react differently to a novel environment. “Bred high responder” (bHR) rats are highly exploratory with a disinhibited, novelty-seeking temperament, including hyperactivity, aggression, and drug-seeking. “Bred low responder” (bLR) rats are highly-inhibited, exhibiting reduced locomotor activity and anxious and depressive-like behavior. These behavioral propensities are robust and stable, beginning early in development similar to temperament in humans. This RNA-sequencing study examined gene expression in the hippocampus, a region critical for emotional regulation, in generation F29 male bHR rats and bLR rats from two ages: P14 and adulthood (n=2/group).
2020-06-02 | GSE140597 | GEO
Project description:The strong pattern of comorbidity amongst psychiatric disorders is believed to be generated by a spectrum of latent liability, arising from a complex interplay of genetic risk and environmental factors, such as stress and childhood adversity. At one end of this spectrum are internalizing disorders, which are associated with neuroticism, anxiety, and depression. At the other end of the spectrum are externalizing disorders, which are associated with risk-taking and novelty-seeking, as seen in mania, substance abuse, and impulse-control disorders. We model the genetic contributions underlying both extremes of this spectrum by selectively breeding rats that react differently to a novel environment. “Bred high responder” (bHR) rats are highly exploratory with a disinhibited, novelty-seeking temperament, including hyperactivity, aggression, and drug-seeking. “Bred low responder” (bLR) rats are highly-inhibited, exhibiting reduced locomotor activity and anxious and depressive-like behavior. These behavioral propensities are robust and stable, beginning early in development similar to temperament in humans. This Affymetrix (Rat Expression Set 230 A) microarray study examined gene expression in the hippocampus in generation F4 adult male bHR rats and bLR rats (n=6 per group).
2020-06-02 | GSE140596 | GEO
Project description:The strong pattern of comorbidity amongst psychiatric disorders is believed to be generated by a spectrum of latent liability, arising from a complex interplay of genetic risk and environmental factors, such as stress and childhood adversity. At one end of this spectrum are internalizing disorders, which are associated with neuroticism, anxiety, and depression. At the other end of the spectrum are externalizing disorders, which are associated with risk-taking and novelty-seeking, as seen in mania, substance abuse, and impulse-control disorders. We model the genetic contributions underlying both extremes of this spectrum by selectively breeding rats that react differently to a novel environment. “Bred high responder” (bHR) rats are highly exploratory with a disinhibited, novelty-seeking temperament, including hyperactivity, aggression, and drug-seeking. “Bred low responder” (bLR) rats are highly-inhibited, exhibiting reduced locomotor activity and anxious and depressive-like behavior. These behavioral propensities are robust and stable, beginning early in development similar to temperament in humans. This Affymetrix (Rat Expression Set 230 A) microarray study examined gene expression in the hippocampus in generation F15 male bHR rats and bLR rats at age postnatal day 14 (P14, n=6 per group).
2020-06-02 | GSE140595 | GEO
Project description:The strong pattern of comorbidity amongst psychiatric disorders is believed to be generated by a spectrum of latent liability, arising from a complex interplay of genetic risk and environmental factors, such as stress and childhood adversity. At one end of this spectrum are internalizing disorders, which are associated with neuroticism, anxiety, and depression. At the other end of the spectrum are externalizing disorders, which are associated with risk-taking and novelty-seeking, as seen in mania, substance abuse, and impulse-control disorders. We model the genetic contributions underlying both extremes of this spectrum by selectively breeding rats that react differently to a novel environment. “Bred high responder” (bHR) rats are highly exploratory with a disinhibited, novelty-seeking temperament, including hyperactivity, aggression, and drug-seeking. “Bred low responder” (bLR) rats are highly-inhibited, exhibiting reduced locomotor activity and anxious and depressive-like behavior. These behavioral propensities are robust and stable, beginning early in development similar to temperament in humans. This Illumina (RatRef-12v1 Beadchip) microarray study examined gene expression in the hippocampus in generation F15 male bHR rats and bLR rats at age postnatal day 14 (P14, n=6 per group).
2020-06-02 | GSE140594 | GEO
Project description:We report 33 microRNAs are differentially expressed in the dorsal raphe and/or amygdala of rats selectively bred for high and low locomotor response to novelty (high responder and low responder rats)
2017-03-12 | GSE86934 | GEO
Project description:The strong pattern of comorbidity amongst psychiatric disorders is believed to be generated by a spectrum of latent liability, arising from a complex interplay of genetic risk and environmental factors, such as stress and childhood adversity. At one end of this spectrum are internalizing disorders, which are associated with neuroticism, anxiety, and depression. At the other end of the spectrum are externalizing disorders, which are associated with risk-taking and novelty-seeking, as seen in mania, substance abuse, and impulse-control disorders. We model the genetic contributions underlying both extremes of this spectrum by selectively breeding rats that react differently to a novel environment. “Bred high responder” (bHR) rats are highly exploratory with a disinhibited, novelty-seeking temperament, including hyperactivity, aggression, and drug-seeking. “Bred low responder” (bLR) rats are highly-inhibited, exhibiting reduced locomotor activity and anxious and depressive-like behavior. These behavioral propensities are robust and stable, beginning early in development similar to temperament in humans. This dataset was part of a larger RNA-Sequencing study examining gene expression in the bHR/bLR hippocampus, a region critical for emotional regulation. The original study compared repeated injections of either antidepressant medication (fluoxetine or desipramine) or vehicle (VEH=1:1 saline and water) solution in bHR and bLR rats (14 days of intraperitoneal injections - P78-P92, 1 per day) under either standard laboratory housing conditions or chronic variable stress. This upload includes only the data from the control subjects: generation F43 adult male bHR VEH rats and bLR VEH rats housed in standard conditions (n=5/group). Prior to sacrifice, at age P92, the rats underwent social interaction testing after 15 minutes of exposure to an anxiogenic environment (the elevated plus maze). The results from the social interaction testing are provided here along with the gene expression data.
2020-06-02 | GSE140287 | GEO
Project description:Hippocampal Gene Expression in bred High Responder (bHR) vs. bred Low Responder (bLR) Rats: RNA-Seq Data from Generation F43
| PRJNA589093 | ENA