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An operant social self-administration and choice model in rats

Nature Protocols volume 15, pages 1542–1559 (2020)Cite this article

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Abstract

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.

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Fig. 1: Social-choice self-administration apparatus.
Fig. 2: Protocol timeline.
Fig. 3: Using the protocol to study incubation of drug craving.
Fig. 4: Generalization of the protocol to Long–Evans rats and remifentanil.
Fig. 5: Using the protocol to study addiction vulnerability.
Fig. 6: Using the protocol to study the motivation to seek operant social rewards.
Fig. 7: Using the protocol to study social seeking.

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Data and code availability

The Med-Associated programs are available from the corresponding authors (M.V. and Y.S.) upon request.

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Acknowledgements

We thank T.I. Russell for her help during the experiments and D. Harvey for proofreading and editorial comments on the original version of the manuscript. The research was supported by the Intramural Research Program of NIDA, a fellowship from the NIH Center on Compulsive Behaviors (M.V.), and a NARSAD Distinguished Investigator Grant Award (Y.S.).

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Authors and Affiliations

  1. Behavioral Neuroscience Research Branch, Intramural Research Program, National Institute on Drug Abuse, National Institutes of Health, Baltimore, MD, USA

    Marco Venniro & Yavin Shaham

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Contributions

M.V. and Y.S. designed the experiments; M.V. ran the experiments and collected the data; M.V. and Y.S. analyzed the data; M.V. and Y.S. wrote the paper.

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Correspondence to Marco Venniro or Yavin Shaham.

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The authors declare no competing interests.

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Peer review information Nature Protocols thanks Francesco Papaleo and the other, anonymous, reviewer(s) for their contribution to the peer review of this work.

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Key references using this protocol

Venniro, M. et al. Nat. Neurosci. 21, 1520–1529 (2018): https://doi.org/10.1038/s41593-018-0246-6

Venniro, M., Russell, T. I., Zhang, M. & Shaham, Y. Biol. Psychiatry 86, 848–856. (2019): https://doi.org/10.1016/j.biopsych.2019.05.018

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Venniro, M., Shaham, Y. An operant social self-administration and choice model in rats. Nat Protoc 15, 1542–1559 (2020). https://doi.org/10.1038/s41596-020-0296-6

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