Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2022 Mar;64(3):e22252.
doi: 10.1002/dev.22252.

Elevated ghrelin alters the behavioral effects of perinatal acetaminophen exposure in rats

Joshua A Herrington  1 , Janet Guss Darwich  1 , Christopher Harshaw  2 , Alev M Brigande  1 , Erica B Leif  1 , Paul J Currie  1
Affiliations

Elevated ghrelin alters the behavioral effects of perinatal acetaminophen exposure in rats

Joshua A Herrington et al. Dev Psychobiol. 2022 Mar.

Abstract

A growing body of evidence links prenatal and early postnatal acetaminophen (APAP) exposure to atypical development of brain and behavior. In adult rodents, APAP is known to produce oxidative stress and lower anxiety-related behavior following acute exposure. In models of early-life exposure, APAP has also been shown to alter anxiety-related and other behaviors. Since the neuropeptide ghrelin has been recently shown to reduce oxidative stress markers and act as a neuroprotectant, we hypothesized that exposure to ghrelin prior to exposure to APAP would mitigate the behavioral effects of APAP exposure. On postnatal day 7, pups were administered doses of either APAP (51.97 mg/kg), ghrelin (1 mg/kg/ml), ghrelin + APAP, or vehicle only. As adults, anxiety-related behavior was assessed in the open field and elevated plus maze. Behavior differed based upon treatment condition. In rats unexposed to ghrelin, APAP treatment resulted in increased exploration (i.e., reduced anxiety) in the open field relative to controls. Rats co-administered APAP and ghrelin did not differ from vehicle-only controls. No significant effects of APAP or interactions between APAP and ghrelin exposures were observed in the elevated plus maze. These results are the first to demonstrate that ghrelin can mitigate the effects of perinatal APAP exposure in rats.

Keywords: acetaminophen; ghrelin; neurodevelopment; neuroprotective; oxidative stress.

PubMed Disclaimer

References

REFERENCES

    1. Akki, R., Raghay, K., & Errami, M. (2021). Potentiality of ghrelin as antioxidant and protective agent. Redox Report, 26, 71-79. https://doi.org/10.1080/13510002.2021.1913374
    1. Alemany, S., Avella-García, C., Liew, Z., García-Esteban, R., Inoue, K., Cadman, T., López-Vicente, M., González, L., Riaño Galán, I., Andiarena, A., Casas, M., Margetaki, K., Strandberg-Larsen, K., Lawlor, D. A., El Marroun, H., Tiemeier, H., Iñiguez, C., Tardón, A., Santa-Marina, L., … Sunyer, J. (2021). Prenatal and postnatal exposure to acetaminophen in relation to autism spectrum and attention-deficit and hyperactivity symptoms in childhood: Meta-analysis in six European population-based cohorts. European Journal of Epidemiology, 36(10), 993-1004. https://doi.org/10.1007/s10654-021-00754-4
    1. Andrews, Z. B., Erion, D., Beiler, R., Liu, Z.-W., Abizaid, A., Zigman, J., Elsworth, J. D., Savitt, J. M., DiMarchi, R., Tschoep, M., Roth, R. H., Gao, X.-B., & Horvath, T. L. (2009). ghrelin promotes and protects nigrostriatal dopamine function via a UCP2-dependent mitochondrial mechanism. Journal of Neuroscience, 29, 14057-14065. https://doi.org/10.1523/JNEUROSCI.3890-09.2009
    1. Anchan, D., Clark, S., Pollard, K., & Vasudevan, N. (2014). GPR30 activation decreases anxiety in the open field test but not in the elevated plus maze test in female mice. Brain and Behavior, 4(1), 51-59. https://doi.org/10.1002/brb3.197
    1. Asakawa, A., Inui, A., Kaga, T., Yuzuriha, H., Nagata, T., Fujimiya, M., Katsuura, G., Makino, S., Fujino, M. A., & Kasuga, M. (2001). A role of ghrelin in neuroendocrine and behavioral responses to stress in mice. Neuroendocrinology, 74, 143-147. https://doi.org/10.1159/000054680

Publication types

LinkOut - more resources