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Hippocampal RNA-Seq Data and Behavioral Data from Rats Selectively-Bred to Show High or Low Levels of Locomotor Activity in a Novel Environment (bred High Responders vs. bred Low Responders)

ABSTRACT: Using selective breeding, we have produced two rat lines with highly contrasting heritable behaviors: bred Low Responders (bLR) are extremely inhibited and anxious in a novel environment, whereas bred High Responders (bHR) are exploratory and sensation-seeking. These traits map onto temperamental extremes predictive of internalizing vs. externalizing psychiatric disorders in humans and can model two divergent paths to drug abuse. To elucidate gene expression underlying these behavioral extremes, bHRxbLR were bred to produce a F0-F1-F2 cross. We then measured exploratory locomotion, anxiety-like behavior, and sensitivity to reward cues (Pavlovian Conditioned Approach) and performed hippocampal RNA sequencing in both F0s (n=24, n=6/phenotype/sex) and F2s (n=250, n=125/sex). The data included in this GEO upload is the data from the F0s from this experiment.

ORGANISM(S): Rattus norvegicus

PROVIDER: GSE225744 | GEO | 2025/02/07

REPOSITORIES: GEO

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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.

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Hippocampal RNA-Seq Data and Behavioral Data from Rats Selectively-Bred to Show High or Low Levels of Locomotor Activity in a Novel Environment (bred High Responders vs. bred Low Responders)

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