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Medial orbitofrontal cortex and nucleus accumbens mediation in risk assessment behaviors in adolescents and adults

Neuropsychopharmacology volume 47, pages 1808–1815 (2022)Cite this article

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Abstract

Risk assessment behaviors are necessary for gathering risk information and guiding decision-making. Risky decision-making heightens during adolescence, possibly as a result of low risk awareness and an increase in sensitivity to reward-associated cues and experiences. Higher adolescent engagement in high-risk behaviors may be, in part, due to developing circuits that contribute to risk assessment behaviors. Nucleus accumbens (NAc) activity is linked to risky decision-making and receives inputs carrying sensory and emotional information. Namely, the medial orbitofrontal cortex (MO) contributes to behavior guided by reward probability and sends direct projections to the NAc (MO→NAc), which may permit risk assessment in a mature circuit. Here, we evaluated risk assessment behaviors in adult and adolescent rats during elevated plus maze (EPM) exploration, including stretch and attend postures, head dips, and rears. We found that adolescents exhibited fewer EPM risk assessment behaviors than adults. We also quantified MO→NAc projections using a fluorescent anterograde tracer, Fluoro-Ruby, in both age groups. Labeled MO→NAc pathways exhibited greater total fluorescence in adults than in adolescents, indicating MO→NAc fibers increase over development. Using a disconnection approach to measure the contribution of the MO-NAc pathway in adults, we found that ipsilateral inactivation of the MO-NAc did not alter risk assessment behavior; however, MO-NAc disconnection reduced the number of stretch-and-attend postures. Together, this work suggests that the development of MO-NAc pathways can contribute to age-dependent differences in risk assessment.

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Fig. 1: Model of the elevated plus maze and quantified risk assessment behaviors.
Fig. 2: Adolescents exhibited fewer elevated plus maze risk assessment behaviors than adults.
Fig. 3: Density of MO projections terminating in the NAc is greater in adults than adolescents.
Fig. 4: Disconnection approach for the inactivation of MO-NAc interactions.
Fig. 5: Disconnection of MO-NAc interactions reduces stretch and attend posture exhibition.

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Acknowledgements

We gratefully acknowledge the help of Eliska Mrackova, Brittany Avonts, and Dr. Ryan Selleck for technical support.

Funding

This work was supported by the National Institutes of Health (MH084970 and MH118237 to J.A.R.). The funding agents did not have a role in study design, collection, analysis, interpretation of data, writing of the report, or in the decision to submit this work for publication.

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  1. Department of Foundational Sciences and Humanities, Cellular and Molecular Pharmacology, Chicago Medical School, Rosalind Franklin University of Medicine and Science, North Chicago, IL, USA

    Maxine K. Loh, Nicole C. Ferrara, Jocelyn M. Torres & J. Amiel Rosenkranz

  2. Center for Neurobiology of Stress Resilience and Psychiatric Disorders, Rosalind Franklin University of Medicine and Science, North Chicago, IL, USA

    Maxine K. Loh, Nicole C. Ferrara, Jocelyn M. Torres & J. Amiel Rosenkranz

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Conceptualization: MKL and JAR; Methodology: MKL, NCF, and JAR; Data Curation: MKL and JMT; Validation: MKL; Analysis: MKL; Resources: JAR; Original Draft preparation: MKL; Draft Revisions & Edits: MKL, NCF, and JAR; Funding Acquisition: JAR.

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Correspondence to Maxine K. Loh.

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Loh, M.K., Ferrara, N.C., Torres, J.M. et al. Medial orbitofrontal cortex and nucleus accumbens mediation in risk assessment behaviors in adolescents and adults. Neuropsychopharmacol. 47, 1808–1815 (2022). https://doi.org/10.1038/s41386-022-01273-w

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