Sex and strain influence attribution of incentive salience to reward cues in mice

Dickson, Price E.; McNaughton, Kathryn; Hou, Lingfeng; Anderson, Laura; Long, Katie H.; Chesler, Elissa J.

doi:10.1016/j.bbr.2015.05.039

Cited by 32 publications

(22 citation statements)

References 39 publications

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“…The observed heritability of impulsivity is also consistent with other traits shown to confer susceptibility to addiction-like behaviors in rodents. Thus, anxiety 35,36 , novelty reactivity 31,37 , novelty preference 38 and incentive salience attribution (sign-vs goal-tracking 39 Table 1. Heritability estimates for premature responding incorporating different random effects (sex, breeding, sex and breeding).…”

Section: Discussionmentioning

confidence: 99%

“…While there is evidence to suggest the heritability of these susceptibility traits are primarily driven by an inter-relationship with novelty reactivity (e.g. 38,39 ), rats impulsive on the 5CSRTT fail to show enhanced measures of novelty reactivity 19,40 . Further, impulsivity and novelty reactivity have been shown to predict distinct aspects of addiction-like behavior 24 suggesting the addiction vulnerability phenotype in rats may involve multiple genetic contributions.…”

Section: Discussionmentioning

confidence: 99%

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Impulsivity is a heritable trait in rodents and associated with a novel quantitative trait locus on chromosome 1

Jupp

Pitzoi

Petretto

et al. 2020

Sci Rep

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Differential gene expression within the identified linkage region in highly-impulsive rats. To identify potential candidate genes within the linkage region we conducted a microarray analysis to investigate differences in transcript levels between HI and LI from both the outbred base population and animals from the sixth generation of the pedigree to identify common alterations in transcriptome expression associated with impulsivity. We investigated transcript expression in the NAcC, NAcS and in the case of sixth generation rats, the ventromedial PFC, or infralimbic cortex (IL) (Fig. 4A). Of the 148 genes within the linkage region represented on the array (Supplementary Table S5), several of these genes were found to be differentially-regulated in HI and LI rats (false discovery rate 10%) based on a non-parametric ranking analysis of the microarray data. A total of 13 transcripts were found to be up-regulated and 16 down-regulated in HI rats of the outbred base population, while 6 transcripts were up-regulated and 7 down-regulated in the F6 generation of HI rats (Table 2). Of these differentially-expressed transcripts, two were found to be consistently differentially-regulated in the same direction, in the same brain region between the two generations examined, Hbb and Nmb (Fig. 4B). After integration of the differential expression findings with the WGS results, we found that some of the differentially-expressed genes were also polymorphic (Pde3b, Sv2b, and Hbb; Supplementary Table S3) or had indels (Sv2b,

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Impulsivity is a heritable trait in rodents and associated with a novel quantitative trait locus on chromosome 1

Jupp

Pitzoi

Petretto

et al. 2020

Sci Rep

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“…Examples include psychotropic drug response [48,49], infectious disease response [50], and transcript splice variation [51] across the founders. The heritability of reward-related behavioral traits that have proved difficult to observe in conventional mouse strains was established in founder strains [52]. However, it should be noted that certain founders may have characteristics precluding specific procedures, whereas their outcrossed progeny and derivative populations may not.…”

Section: Establishing Trait Heritability In the Foundersmentioning

confidence: 99%

High-Diversity Mouse Populations for Complex Traits

et al. 2019

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Contemporary mouse genetic reference populations are a powerful platform to discover complex disease mechanisms. Advanced high-diversity mouse populations include the Collaborative Cross (CC) strains, Diversity Outbred (DO) stock, and their isogenic founder strains. When used in systems genetics and integrative genomics analyses, these populations efficiently harnesses known genetic variation for precise and contextualized identification of complex disease mechanisms. Extensive genetic, genomic, and phenotypic data are already available for these high-diversity mouse populations and a growing suite of data analysis tools have been developed to support research on diverse mice. This integrated resource can be used to discover and evaluate disease mechanisms relevant across species. The Challenge of Complex Disease Complex diseases present compelling biomedical challenges that can be studied using human and nonhuman animal genetics. Although advances in human genetics have identified loci for many heritable complex diseases [1-8], there are several well-known limitations of genomewide association studies (GWASs). (i) For many human disease loci, the biological mechanism of action is unknown. (ii) When little is known about a locus, the path from genetic association to clinically actionable targets is unclear. (iii) Disease process or developmental trajectory is not always obvious from a causal genetic variant. (iv) GWAS results may not generalize across human subpopulations. (v) Medical records and participant phenotyping is often incomplete, imprecise, and retrospective, whereas model organism phenotyping can include in-depth, prospective, and standardized measures. (vi) Sample size requirements are formidable in human GWASs. (vii) Power is insufficient to study interacting genetic loci. (viii) Studies of genetic interaction with development, environment, and sex are largely intractable. Further, heterogeneous diseases like psychiatric disorders manifest with overlapping symptoms, intertwined disease trajectories [9], and complex genetic regulation [9,10]. In summary, the SNP-to-disease association model underlying GWASs cannot readily capture complex disease biology without further biological context. These challenges are often tractable with discovery genetics in model organisms.

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“…Despite their similarities, however, sexual and nonsexual social rewards have distinct valences and motivational properties (Trezza et al, 2011). Also, our results demonstrate that STs can attribute incentive-motivational value to more than one CS (e.g., a lever-CS predicting food delivery and a star-CS predicting social interaction), and behaviors related to sign-tracking (increased novelty-seeking and CPP) are consistent across different stimuli and procedures (Dickson et al, 2015. Finally, this study is the first to demonstrate individual variation in social behaviors in an outbred rodent population.…”

Section: Discussionmentioning

confidence: 59%

Individual variation in the attribution of incentive salience to social cues

Fitzpatrick

Morrow

2019

Preprint

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Research on the attribution of incentive salience to drug cues has furthered our understanding of drug self-administration in animals as well as drug relapse and craving in humans. The influence of peers and other social cues on drug-seeking has garnered more attention recently, but few studies have investigated the ability of social cues to gain incentivemotivational value. In the present study, a Pavlovian conditioned approach procedure was used to identify rats that are more (sign-trackers) or less (goal-trackers) prone to attribute incentive salience to food reward cues. A novel procedure then employed social 'peers' to compare the tendency of sign-trackers and goal-trackers to attribute incentive salience to social reward cues.Social behavior of sign-trackers and goal-trackers was also compared using social interaction and choice tests. Finally, basal levels of plasma oxytocin were measured in sign-trackers and goaltrackers, because oxytocin is known to modulate the mesolimbic reward system and social behavior. Compared to goal-trackers, sign-trackers attributed more incentive salience to social cues and exhibited more prosocial behaviors. No group differences were observed in baseline plasma oxytocin levels. Taken together, these experiments demonstrate a concordance of individual variation in social behavior, the attribution of incentive salience to social cues following peer interaction, and attribution of incentive salience to food cues. This general tendency to attribute motivational value to reward cues has important implications for the pathophysiology of addiction and other disorders of reward learning.

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Sex and strain influence attribution of incentive salience to reward cues in mice

Cited by 32 publications

References 39 publications

Impulsivity is a heritable trait in rodents and associated with a novel quantitative trait locus on chromosome 1

Impulsivity is a heritable trait in rodents and associated with a novel quantitative trait locus on chromosome 1

High-Diversity Mouse Populations for Complex Traits

Individual variation in the attribution of incentive salience to social cues

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