Selective Breeding for Divergence in Novelty-seeking Traits: Heritability and Enrichment in Spontaneous Anxiety-related Behaviors
Abstract
Outbred Sprague-Dawley rats can be classified as high responders (HR) or low responders (LR) based on their levels of exploratory locomotion in a novel environment. While this novelty-seeking dimension was originally related to differential vulnerability to substance abuse, behavioral, neuroendocrine and gene expression studies suggest a fundamental difference in emotional reactivity between these animals. Here, we report the first study to selectively breed rats based on this novelty-seeking dimension. Response to novelty was clearly heritable, with a > 2-fold difference in behavior seen after eight generations of selection. Three tests of anxiety-like behavior consistently showed significantly greater anxiety in LR-bred rats compared to HR-bred animals, and this difference was diminished in the open field test by administration of the anxiolytic benzodiazepine drug, chlordiazepoxide. Cross-fostering revealed that responses to novelty were largely unaffected by maternal interactions, though there was an effect on anxiety-like behavior. These selected lines will enable future research on the interplay of genetic, environmental and developmental variables in controlling drug seeking behavior, stress and emotional reactivity.
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In rats selectively-bred for differences in locomotor responses to a novel environment, high responders to novelty (bHR) consistently learn a sign-tracking CR but low responders to novelty (bLR) consistently learn a goal-tracking CR.
“In rats selectively-bred for differences in locomotor responses to a novel environment14, high responders to novelty (bHR) consistently learn a sign-tracking CR but low responders to novelty (bLR) consistently learn a goal-tracking CR15.”
From A selective role for dopamine in stimulus-reward learning (2011) · cites this paper as [15]
The extent to which a predictor of reward acquires incentive value differs between individuals.
“However, the extent to which a predictor of reward acquires incentive value differs between individuals, providing the opportunity to parse the role of dopamine in stimulus-reward learning”
From A selective role for dopamine in stimulus-reward learning (2011) · cites this paper as [15]
In these lines, unlike the case in outbred rats, there is a strong correlation between locomotor response to novelty and the tendency to sign-track.
“Moreover in these lines, unlike the case in outbred rats13,28, there is a strong correlation between locomotor response to novelty and the tendency to sign-track15.”
From A selective role for dopamine in stimulus-reward learning (2011) · cites this paper as [15]
When presentation of a lever-CS was paired with food delivery, both bHRs and bLRs developed a Pavlovian CR, but the topography of the CR was different in the two groups.
“When presentation of a lever-CS was paired with food delivery both bHRs and bLRs developed a Pavlovian CR, but as we have described previously15, the topography of the CR was different in the two groups.”
From A selective role for dopamine in stimulus-reward learning (2011) · cites this paper as [15]
The selectively-bred rats used in this study have distinctive behavioral phenotypes, including greater behavioral disinhibition and reduced impulse control in bHRs.
“The selectively-bred rats used in this study have distinctive behavioral phenotypes, including greater behavioral disinhibition and reduced impulse control in bHRs15.”
From A selective role for dopamine in stimulus-reward learning (2011) · cites this paper as [15]
These behavioral phenotypes are accompanied by baseline differences in dopamine transmission, with bHRs showing elevated sensitivity to dopamine agonists, increased proportion of striatal D2 receptors in a high-affinity state, greater frequency of spontaneous dopamine transients, and higher reward-related dopamine release prior to conditioning.
“These behavioral phenotypes are accompanied by baseline differences in dopamine transmission, with bHRs showing elevated sensitivity to dopamine agonists, increased proportion of striatal D2receptors in a high-affinity state, greater frequency of spontaneous dopamine transients15, and higher reward-related dopamine release prior to conditioning, all of which could enhance their attribution of in”
From A selective role for dopamine in stimulus-reward learning (2011) · cites this paper as [15]
Individuals who attribute reward cues with incentive salience find it more difficult to resist such cues, a feature associated with reduced impulse control.
“Individuals who attribute reward cues with incentive salience find it more difficult to resist such cues, a feature associated with reduced impulse control15,31.”
From A selective role for dopamine in stimulus-reward learning (2011) · cites this paper as [15]
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References 36 · Cited by 209
- Authors
- Stead, J. D. H., Clinton, S., Neal, C., Schneider, J., Jama, A., Miller, S., Vazquez, D. M., Watson, S. J., & Akil, H.
- Affiliations
- Carleton University (CA)
- University of Michigan (US)
- University of Hawaiʻi at Mānoa (US)
- Corresponding author
- Stead, John D. H.
- Venue
- Behavior Genetics
- Published
- 2006-02-24
- Volume
- 36
- Issue
- 5
- Pages
- 697-712
- ISSN
- 0001-8244 (ISSN-L)
- 1573-3297
- OpenAlex
- W1972499031
- Cited by
- 209
- References
- 36
- Citations by year
- 2026: 3 · 2025: 4 · 2024: 9 · 2023: 4 · 2022: 12 · 2021: 8 · 2020: 12 · 2019: 11 · 2018: 12 · 2017: 8 · 2016: 12 · 2015: 11 · 2014: 6 · 2013: 15 · 2012: 10
- FWCI
- 5.56
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Behavior Genetics (publishedVersion)
- PubMed (publishedVersion)
- Deep Blue (University of Michigan) (acceptedVersion)
- Funders
- National Institute of Mental Health (P01 MH 42251, P01MH042251)
- National Institute on Drug Abuse (R01 DA13386, R01DA013386)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
- Life Sciences › Agricultural and Biological Sciences › Ecology, Evolution, Behavior and Systematics › Animal Behavior and Reproduction
- Keywords
- novelty seeking, selective breeding, heritability, anxiety-like behavior, exploratory locomotion, Sprague-Dawley rats, chlordiazepoxide, cross-fostering, maternal effects, emotional reactivity
- MeSH terms
- Animals, Anxiety, Behavior, Animal, Breeding, Darkness, Exploratory Behavior, Genetics, Behavioral, Humans, Light, Motor Activity, Reproduction, Genetic Variation, Rats, Sprague-Dawley, Maze Learning, Rats
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