The sensation seeking trait confers a dormant susceptibility to addiction that is revealed by intermittent cocaine self-administration in rats

• Published in: Neuropharmacology 2021-09, Vol.195, p.108566-108566, Article 108566
• Main Authors: O'Connor, Shayna L., Aston-Jones, Gary, James, Morgan H.
• Format: Article
• Language: English
• Subjects: Animals; Behavior, Animal - drug effects; Behavioral economics; Cocaine - administration & dosage; Cocaine prime; Cocaine-Related Disorders - physiopathology; Demand elasticity; Dopamine Uptake Inhibitors - administration & dosage; Drug-Seeking Behavior - drug effects; Male; Motor Activity - drug effects; Novelty seeking; Rats; Rats, Sprague-Dawley; Self Administration; State vs trait
• ISSN: 0028-3908; 1873-7064
• DOI: 10.1016/j.neuropharm.2021.108566

Heightened sensation seeking is associated with an increased risk of substance use disorder in clinical populations. In rats, sensation seeking is often examined by measuring locomotor reactivity to a novel environment. So-called high responders (HR) acquire self-administration of psychostimulants more quickly and consume higher amounts of drug compared to low responder (LR) rats, indicating that the HR trait might confer a stronger addiction propensity. However, studies of addiction-like behaviors in HR vs LR rats have typically utilized self-administration paradigms that do not dissociate individual differences in the hedonic/reinforcing and motivational properties of a drug. Moreover, little attention has been given to whether HR rats are more susceptible to drug-access conditions that promote a state-dependent addiction phenotype. We report that on a behavioral economics task, HR rats have higher preferred brain-cocaine levels compared to LR rats but do not differ with respect to their demand elasticity for cocaine. In contrast, when tested on an intermittent access schedule of cocaine self-administration, which has been shown to promote several addiction-related endophenotypes, HR rats exhibit greater escalation of intake and more drastic reductions in cocaine demand elasticity. Together, these data indicate that the HR trait does not confer higher extant addiction behavior, but rather that this phenotype is associated with a propensity for addiction that remains dormant until it is actuated by intermittent drug intake. These findings reveal a ‘trait’ (HR) by ‘state’ (intermittent drug intake) interaction that produces a strong addiction-like phenotype. This article is part of the special issue on ‘Vulnerabilities to Substance Abuse'. •High locomotor responsivity (HR) to a novel environment is an index of sensation seeking.•Limited cocaine access reveals higher null-cost cocaine demand in HR rats but no difference in elasticity.•Intermittent access (IntA) to cocaine reveals greater propensity to escalate intake in HR rats.•HR rats also exhibit greater reductions in cocaine demand elasticity after IntA.•These data point to a trait (HR) x state (IntA) interaction in the development of addiction.