Individual differences in addiction-like behaviors and choice between cocaine versus food in Heterogeneous Stock rats

Psychopharmacology (Berl). 2021 Dec;238(12):3423-3433. doi: 10.1007/s00213-021-05961-1. Epub 2021 Aug 20.


Rationale and objectives: Recent studies reported that when given a mutually exclusive choice between cocaine and palatable food, most rats prefer the non-drug reward over cocaine. However, these studies used rat strains with limited genetic and behavioral diversity. Here, we used a unique outbred strain of rats (Heterogeneous Stock, HS) that mimic the genetic variability of humans.

Methods: We first identified individual differences in addiction-like behaviors (low and high). Next, we tested choice between cocaine and palatable food using a discrete choice procedure. We characterized the individual differences using an addiction score that incorporates key features of addiction: escalated intake, highly motivated responding (progressive ratio), and responding despite adverse consequences (footshock punishment). We assessed food versus cocaine choice at different drug-free days (without pre-choice cocaine self-administration) during acquisition of cocaine self-administration or after escalation of cocaine self-administration. We also assessed drug versus food choice immediately after 1-, 2-, or 6-h cocaine self-administration.

Results: Independent of the addiction score, without pre-choice cocaine (1 or more abstinence days), HS rats strongly preferred the palatable food over cocaine, even if the food reward was delayed or its size was reduced. However, rats with high but not low addiction score modestly increased cocaine choice immediately after 1-, 2-, or 6-h cocaine self-administration.

Conclusions: Like other strains, HS rats strongly prefer palatable food over cocaine. Individual differences in addiction score were associated with increased drug choice in the presence but not absence (abstinence) of cocaine. The HS strain may be useful in studies on mechanisms of addiction vulnerability.

Keywords: Addiction; Discrete choice; Individual differences; Intoxication; Natural reward; Preference; Self-administration.

MeSH terms

  • Animals
  • Behavior, Addictive*
  • Cocaine*
  • Cocaine-Related Disorders*
  • Individuality
  • Rats
  • Reward
  • Self Administration


  • Cocaine