An operant social self-administration and choice model in rats

Nat Protoc. 2020 Apr;15(4):1542-1559. doi: 10.1038/s41596-020-0296-6. Epub 2020 Mar 20.


It is difficult to translate results from animal research on addiction to an understanding of the behavior of human drug users. Despite decades of basic research on neurobiological mechanisms of drug addiction, treatment options remain largely unchanged. A potential reason for this is that mechanistic studies using rodent models do not incorporate a critical facet of human addiction: volitional choices between drug use and non-drug social rewards (e.g., employment and family). Recently, we developed an operant model in which rats press a lever for rewarding social interaction with a peer and then choose between an addictive drug (heroin or methamphetamine) and social interaction. Using this model, we showed that rewarding social interaction suppresses drug self-administration, relapse to drug seeking, and brain responses to drug-associated cues. Here, we describe a protocol for operant social interaction using a discrete-trial choice between drugs and social interaction that causes voluntary abstinence from the drug and tests for incubation of drug craving (the time-dependent increase in drug seeking during abstinence). This protocol is flexible but generally requires 8-9 weeks for completion. We also provide a detailed description of the technical requirements and procedures for building the social self-administration and choice apparatus. Our protocol provides a reliable way to study the role of operant social reward in addiction and addiction vulnerability in the context of choices. We propose that this protocol can be used to study brain mechanisms of operant social reward and potentially impairments in social reward in animal models of psychiatric disorders and pain.

Publication types

  • Research Support, N.I.H., Intramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Choice Behavior / physiology*
  • Conditioning, Operant / physiology*
  • Disease Models, Animal
  • Drug-Seeking Behavior / physiology*
  • Female
  • Heroin / administration & dosage
  • Male
  • Methamphetamine / administration & dosage
  • Models, Psychological*
  • Rats
  • Rats, Long-Evans
  • Rats, Sprague-Dawley
  • Remifentanil / administration & dosage
  • Self Administration / methods*
  • Social Behavior
  • Substance-Related Disorders / psychology


  • Methamphetamine
  • Heroin
  • Remifentanil