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The protective effect of operant social reward on cocaine self-administration, choice, and relapse is dependent on delay and effort for the social reward

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Abstract

Social reinforcement-based treatments are effective for many, but not all, people with addictions to drugs. We recently developed an operant rat model that mimics features of one such treatment, the community-reinforcement approach. In this model, rats uniformly choose social interaction over methamphetamine or heroin. Abstinence induced by social preference protects against the incubation of drug-seeking that would emerge during forced abstinence. Here, we determined whether these findings generalize to cocaine and whether delaying or increasing effort for social interaction could reveal possibly human-relevant individual differences in responsiveness. We trained male and female rats for social self-administration (6 days) and then for cocaine self-administration, initially for 2-h/day for 4 days, and then for 12-h/day continuously or intermittently for 8 days. We assessed relapse to cocaine seeking after 1 and 15 days. Between tests, the rats underwent either forced abstinence or social-choice-induced abstinence. After establishing stable social preference, we manipulated the delay for both rewards or for social reward alone, or the response requirements (effort) for social reward. Independent of cocaine-access conditions and sex, operant social interaction inhibited cocaine self-administration and prevented incubation of cocaine seeking. Preference for social access was decreased by the delay of both rewards or social reward alone, or by increased response requirements for social reward, with notable individual variability. This choice procedure can identify mechanisms of individual differences in an animal model of cocaine use and could thereby help screen medications for people who are relatively unresponsive to treatments based on rewarding social interaction.

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Fig. 1: Social-choice-induced voluntary abstinence inhibits incubation of cocaine craving after continuous self-administration access.
Fig. 2: Social-choice-induced voluntary abstinence inhibits incubation of cocaine craving after intermittent self-administration access.
Fig. 3: Delay of social reward, or increased effort to obtain the social reward, increased cocaine preference, with considerable inter-individual variability.

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Funding

The authors declare that they do not have any conflicts of interest (financial or otherwise) related to the text of the paper. The research was supported by the Intramural Research Program of NIDA, a grant from NIDA [DA047976] (MV), and the NARSAD Distinguished Investigator Grant Award (YS).

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MV, LVP, DHE and YS contributed to different aspects of the study, including the design and performance of the research, the data analysis, and the write-up of the paper.

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Correspondence to Marco Venniro or Yavin Shaham.

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Venniro, M., Panlilio, L.V., Epstein, D.H. et al. The protective effect of operant social reward on cocaine self-administration, choice, and relapse is dependent on delay and effort for the social reward. Neuropsychopharmacol. 46, 2350–2357 (2021). https://doi.org/10.1038/s41386-021-01148-6

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