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 a large population of 2716 outbred heterogeneous stock rats. We then determined whether this was associated with performance in 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.

Highly processed foods can be considered addictive substances based on established scientific criteria

“…From this extensive literature, we know that animals will self-administer HPF in a much wider range of conditions than nicotine; in fact, it is often the behavior trained first before attempting to train an animal to self-administer a drug [91]. Cues presented with HPFs rapidly become secondary reinforcers and places where HPFs are administered become strongly preferred [92][93][94]. The ability of HPFs to rapidly deliver refined carbohydrates, fat and sweet tastes appears to play a key role in their reinforcing nature, as these factors are all highly reinforcing even when studied in isolation [95][96][97].…”

Dorsomedial Striatum CB1R signaling is required for Pavlovian outcome devaluation in male Long Evans rats and reduces inhibitory synaptic transmission in both sexes

“…After extended training (>10 session), both GT and ST rats show sensitivity to satiety-induced outcome devaluation [9], an effect established in male rats. Female rats show increased levels of sign-tracking, or lever-directed approach during PLA compared to males [12,13,22,[25][26][27], suggesting they may be less sensitive to outcome devaluation even after extended training. Here we evaluate sex differences in behavioral flexibility using the sign-tracking model and determine whether DMS CB1R signaling contributes to individual and sex differences in devaluation sensitivity after extended Pavlovian training.…”

“…After extended training (>10 session), both GT and ST rats show sensitivity to satietyinduced outcome devaluation (Keefer et al, 2020), an effect established in male rats. Female rats show increased levels of sign-tracking, or lever-directed approach during PLA compared to males (Hammerslag and Gulley, 2014;Keefer et al, 2022;King et al, 2020;Kochli et al, 2020;Madayag et al, 2017;Pitchers et al, 2015), suggesting they may be less sensitive to outcome devaluation even after extended training. In the present study, we use intracranial CB1R inverse agonist, rimonabant, to determine the role of DMS CB1R in mediating Pavlovian devaluation sensitivity in male and female rats.…”