Incentive salience attribution, “sensation-seeking” and “novelty-seeking” are independent traits in a large sample of male and female heterogeneous stock rats

Abstract

There are a number of traits that are thought to increase susceptibility to addiction, and some of these are modeled in preclinical studies. For example, "sensation-seeking" is predictive of the initial propensity to take drugs; whereas "novelty-seeking" predicts compulsive drug-seeking behavior. In addition, the propensity to attribute incentive salience to reward cues can predict the propensity to approach drug cues, and reinstatement or relapse, even after relatively brief periods of drug exposure. The question addressed here is the extent to which these three 'vulnerability factors' are related; that is, predictive of one another. Some relationships have been reported in small samples, but here a large sample of 1,598 outbred male and female heterogeneous stock rats were screened for Pavlovian conditioned approach behavior (to obtain an index of incentive salience attribution; 'sign-tracking'), and subsequently tested for sensation-seeking and novelty-seeking. Despite the large N there were no significant correlations between these traits, in either males or females. There were, however, novel relationships between multiple measures of incentive salience attribution and, based on these findings, we generated a new metric that captures "incentive value". Furthermore, there were sex differences on measures of incentive salience attribution and sensation-seeking behavior that were not previously apparent.

Bioenergetic-Related Gene Expression in the Hippocampus Predicts Internalizing vs. Externalizing Behavior in a F2Cross of Selectively-Bred Rats

“…Sign-trackers are more responsive to both food and drug conditioned stimuli and are prone to addiction-related behaviors, as previously shown in our colony, with male bHRs being sign-trackers and bLRs being goal-trackers (Flagel et al, 2011). Our discovery that there are sex differences in ST and GT behavior parallels previous data showing that typical female Sprague-Dawley rats exhibit faster acquisition of PavCA behavior than males (Pitchers et al, 2015), and female heterogeneous stock rats are more likely to be STs than males (Hughson et al, 2019). Previous data also demonstrate that female bHRs acquire cocaine self-administration significantly faster than male bHRs and all bLRs (Davis et al, 2008), suggesting that the sex differences that we observe in PavCA behavior may more broadly reflect sex differences in reward processing.…”

“…This is consistent with the results from our GWAS (Chitre et al, 2022), from which we used a subset of F2 intercross animals for transcriptional profiling (N=250 of 323). The strong correlation between exploratory locomotion and PavCA behavior is unique to our F2 intercross animals as typical outbred rats do not show such a relationship between exploratory locomotion and ST/GT behavior (Flagel et al, 2010; Hughson et al, 2019; T. E. Robinson & Flagel, 2009).…”

Genome-Wide Association Study in a Rat Model of Temperament Identifies Multiple Loci for Exploratory Locomotion and Anxiety-Like Traits

“…Although PavCA traits exhibit low SNP heritability as has been reported for Sprague-Dawley rats (Gileta et al, 2022), they are strongly correlated with EL traits in our F 2 animals, and the genetic correlations are especially strong. This is notable as outbred rats have not shown such a relationship between EL and sign-tracking/goal-tracking behavior (Flagel et al, 2010; Hughson et al, 2019; Robinson & Flagel, 2009). As previously suggested (Flagel et al, 2010), it appears the selective breeding co-selected the sign-tracking/goal-tracking trait along with the sensation-seeking trait, and the present findings point to the genetic features of this association.…”

Alcohol Sensitivity as an Endophenotype of Alcohol Use Disorder: Exploring Its Translational Utility between Rodents and Humans

“…Both RI panels and heterogeneous stocks [ 94 , 108 , 109 , 110 , 111 , 112 , 113 , 114 , 115 , 116 , 117 , 118 , 119 ] have been extensively studied for alcohol-related phenotypes. Furthermore all of these populations have been successfully used to map genes associated with psychiatric traits [ 63 , 91 , 100 , 101 , 120 , 121 , 122 , 123 , 124 ] including addiction-related phenotypes [ 125 ]. It should be noted that the same advances in genotyping technologies that made human GWAS possible have also revolutionized rodent genetics.…”