Sensitivity to food and cocaine cues are independent traits in a large sample of heterogeneous stock rats

Abstract

Sensitivity to cocaine and its associated stimuli (“cues”) are important factors in the development and maintenance of addiction. Rodent studies suggest that this sensitivity is related, in part, to the propensity to attribute incentive salience to food cues, which, in turn, contributes to the maintenance of cocaine self-administration, and cue-induced relapse of drug-seeking. Whereas each of these traits has established links to drug use, the relatedness between the individual traits themselves has not been well characterized in preclinical models. To this end, the propensity to attribute incentive salience to a food cue was first assessed in two distinct cohorts of 2716 outbred heterogeneous stock rats (HS; formerly N:NIH). We then determined whether each cohort was associated with performance in one of two paradigms (cocaine conditioned cue preference and cocaine contextual conditioning). These measure the unconditioned locomotor effects of cocaine, as well as conditioned approach and the locomotor response to a cocaine-paired floor or context. There was large individual variability and sex differences among all traits, but they were largely independent of one another in both males and females. These findings suggest that these traits may contribute to drug-use via independent underlying neuropsychological processes.

Genome-Wide Association Study on Three Behaviors Tested in an Open Field in Heterogeneous Stock Rats Identifies Multiple Loci Implicated in Psychiatric Disorders

“…Prior study mapped several anxiety-like traits using zero maze ( 23 ). GWAS using HS to study behavioral regulation ( 108 ), response to cocaine cues ( 109 ), cocaine ( 110 ), nicotine ( 28 , 81 ), or oxycodone ( 111 ) self-administration are underway. Our study adds to the literature 30 QTLs and 17 candidate genes for psychiatric related behavioral traits.…”

Dopamine Circuit Mechanisms of Addiction-Like Behaviors

“…This represents a challenge for animal models, where the comparatively limited genetic diversity of research subjects may elide some variability factors. Recent work has made use of “heterogeneous stock” rodents – the product of multiple strain crossings - to increase genetic diversity and investigate individual differences in addiction-like behavior and reward learning in the context of drug use ( Hughson et al, 2019 ; de Guglielmo et al, 2021 ; King et al, 2021 ; Sedighim et al, 2021 ). One such study identified a relationship between gut bacterial content and behavioral features of impulsivity and attention ( Peterson et al, 2020 ).…”

Genomic Loci Influencing Cue-Reactivity in Heterogeneous Stock Rats

“…The primary findings, results, and conclusions presented in this paper address a different scientific question than those presented in King et al 2021.…”

“…For Conditioned Reinforcement (CRf) the primary measures were total active and inactive responses, total earned lever reinforcers, total lever deflections, and an incentive value index ((responses in active port − responses in inactive port) / lever contacts). We chose to separately examine total lever deflections and lever deflections corrected for total responses, because we have previously shown that these measures are more strongly correlated to the PavCA index (Hughson et al, 2019; King et al, 2021).…”