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Developmental and behavioral effects in neonatal and adult mice following prenatal activation of endocannabinoid receptors by capsaicin

Acta Pharmacologica Sinicavolume 40pages418424 (2019) | Download Citation



Despite the apparent abundance of ligand-gated transient receptor potential vanilloid type 1 (TRPV1) and possible cross talk between the endocannabinoid and endovanilloid systems in the central nervous system (CNS), it is unclear what role TRPV1 receptor activation in CNS plays in neurobehavioral development. We previously reported that capsaicin or WIN55212-2 induces risk aversion in the plus-maze test, which was dependent on the gender and mouse strain used. In this study, pregnant BALBc mice were administered capsaicin (1.0 or 4.0 mg/kg, i.p.) during the second week of gestation. Developmental effects of prenatal exposure to capsaicin were assessed in neonates, and behavioral effects were assessed in adult offspring. Gender- and dose-specific variations in ultrasonic vocalizations, weight gain, righting reflex, and general activity of the pups were observed. Prenatal exposure to capsaicin altered plus-maze performance, especially with further exogenous capsaicin challenge. Furthermore, dose- and gender-specific effects were evident in the conditioned place preference/aversion paradigm following conditioning with capsaicin in adult animals. The capsaicin-induced aversion in the plus-maze test was enhanced by WIN55212-2 and blocked by pretreatment with vanilloid antagonist capsazepine or the CB1 receptor antagonist rimonabant, demonstrating an interaction between the endocannabinoid and endovanilloid systems in CNS. Taken together, the interaction between the endocannabinoid and endovanilloid signaling systems can be exploited for therapeutic applications in health and disease.

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AP, SMB, AC-A, ZM, LT, NS, GGG, and ESO are supported by William Paterson University. AC-A is also currently supported by the Mexican National Council of Science and Technology (CONACYT # CVU332502/232728). ESO was supported by NIH grant DA032890. GGG is now at the University of Texas Health Science Center in San Antonio and is supported by grants from DoD #AR110109 as well as by the Morrison Trust, and Lindow, Stephens and Treat, LLP. This is dedicated to the memory of the sudden tragic death of our co-author NS.

Author contributions

ESO conceptualized the study and wrote the manuscript. AP, SMB, AC-A, ZM, LT, NS, GGG, and ESO contributed expertise and support in performing the experiments. NJ revised the figures and NJ and GGG revised the manuscript. All authors approved the publication of this manuscript.

Author information


  1. Department of Biology, William Paterson University, Wayne, NJ, 07403, USA

    • Alex Perchuk
    • , Sonya M. Bierbower
    • , Ana Canseco-Alba
    • , Zoila Mora
    • , Lauren Tyrell
    • , Neal Joshi
    • , Norman Schanz
    •  & Emmanuel S. Onaivi
  2. Center for Biomedical Neuroscience, University of Texas Health Science Center at San Antonio, San Antonio, TX, 78229, USA

    • Georgianna G. Gould


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The authors declare that they have no conflict of interest.

Corresponding author

Correspondence to Emmanuel S. Onaivi.

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