# The protective effect of volitional social interaction on drug addiction

> **NIH NIH R00** · UNIVERSITY OF MARYLAND BALTIMORE · 2021 · $249,000

## Abstract

Project Summary
 Despite strides towards understanding circuit and molecular mechanisms of addiction, treatment options
remain largely unchanged. This impasse is at least partly due to limitations in the construct and predictive
validity of animal models of addiction, which rarely incorporate social factors. In both humans and laboratory
animals, adverse social interactions and social isolation promote drug self-administration and relapse, while
social interactions tend to be protective. I recently developed an operant rat model of choice between drugs
and social interaction and showed the profound protective effects of the latter on addiction. My research
revealed two major findings: (1) rats strongly prefer operant social interaction over drugs, and (2) social choice-
induced voluntary abstinence prevents incubation of methamphetamine (Meth) craving. This protective effect
was associated with activation of PKCδ in central amygdala lateral part (CeL) (assessed by double-labeling of
Fos with PKCδ). In contrast, after homecage forced abstinence, incubation of craving was associated with
selective recruitment of CeL-somatostatin (SOM) neurons. Therefore, the aim of this proposal is to study (1)
the circuit mechanisms underlying the protective effect of social reward on incubation of Meth craving, and (2)
the neural encoding mechanisms of the social interaction versus Meth choice. During the K99 phase, I will
investigate a CeL mechanism of the protective effect of social reward on incubation of Meth craving. This will
be achieved using shRNAs viral constructs to selectively knockdown PKCδ or SOM recently developed by my
collaborator Dr. Messing. Additionally, under the guidance of Dr. Schoenbaum (my co-mentor), I will use
single-unit recording to investigate the neural substrates underlying the preference for social reward over Meth.
I will focus on the orbitofrontal cortex because of its critical role in associative learning and decision-making.
During the R00 phase, I will use the techniques I have learned during my post-doctoral training and the K99
phase to further characterize the circuit mechanisms of the protective effect of social interaction on incubation
of drug craving and drug choice. The proposed training will allow me to develop a future independent research
program geared towards identifying mechanisms underlying the role of social factors in drug addiction.

## Key facts

- **NIH application ID:** 10355849
- **Project number:** 4R00DA047976-02
- **Recipient organization:** UNIVERSITY OF MARYLAND BALTIMORE
- **Principal Investigator:** Marco Venniro
- **Activity code:** R00 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $249,000
- **Award type:** 4N
- **Project period:** 2021-05-01 → 2024-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10355849

## Citation

> US National Institutes of Health, RePORTER application 10355849, The protective effect of volitional social interaction on drug addiction (4R00DA047976-02). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10355849. Licensed CC0.

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