TYPE Original Research PUBLISHED 29 September 2022 DOI 10.3389/fnbeh.2022.982811 OPEN ACCESS EDITED BY Simon Pieraut, University of Nevada, Reno, United States REVIEWED BY Nicole Ferrara, Rosalind Franklin University of Medicine and Science, United States Giovanni Laviola, National Institutes of Health (ISS), Italy *CORRESPONDENCE Jelena Podgorac jelena.podgorac@ibiss.bg.ac.rs SPECIALTY SECTION This article was submitted to Individual and Social Behaviors, a section of the journal Frontiers in Behavioral Neuroscience RECEIVED 30 June 2022 ACCEPTED 31 August 2022 PUBLISHED 29 September 2022 CITATION Podgorac J, Sekuli ´ c S, Petkovi ´ c B, Stojadinovi ´ c G, Marta ´ c L and Peši ´ cV (2022) The influence of continuous prenatal exposure to valproic acid on physical, nociceptive, emotional and psychomotor responses during adolescence in mice: Dose-related effects within sexes. Front. Behav. Neurosci. 16:982811. doi: 10.3389/fnbeh.2022.982811 COPYRIGHT © 2022 Podgorac, Sekuli ´ c, Petkovi ´ c, Stojadinovi ´ c, Marta ´ c and Peši ´ c. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. The influence of continuous prenatal exposure to valproic acid on physical, nociceptive, emotional and psychomotor responses during adolescence in mice: Dose-related effects within sexes Jelena Podgorac 1 *, Slobodan Sekuli ´ c 2,3 , Branka Petkovi ´ c 1 , Gordana Stojadinovi ´ c 1 , Ljiljana Marta ´ c 1 and Vesna Peši ´ c 4 1 Department of Neurophysiology, Institute for Biological Research “Siniša Stankovi´c” – National Institute of the Republic of Serbia, University of Belgrade, Belgrade, Serbia, 2 Faculty of Medicine Novi Sad, University of Novi Sad, Novi Sad, Serbia, 3 Department of Neurology, Clinical Center of Vojvodina, Novi Sad, Serbia, 4 Department of Neurobiology, Institute for Biological Research “Siniša Stankovi´c” – National Institute of the Republic of Serbia, University of Belgrade, Belgrade, Serbia Clinical findings show that the use of valproic acid (VPA) during pregnancy increases the risk of birth defects and autism spectrum disorder in offspring. Although there is a consensus that monitoring of potential long-term outcomes of VPA exposure is needed, especially in undiagnosed individuals, preclinical studies addressing this issue are rare. The present study examined the effects of continuous intrauterine exposure to a wide dose range of VPA (50, 100, 200, and 400 mg/kg/day) on the physical and behavioral response in peripubertal mice as a rodent model of adolescence. Body weight and the hot plate test [on postnatal days (PND) 25 and 32], the elevated plus- maze test (on PND35), and the open field test (on PND40) served to examine physical growth, the supraspinal reflex response to a painful thermal stimulus and conditional learning, anxiety-like/risk-assessment behavior, as well as novelty-induced psychomotor activity, respectively. VPA exposure produced the following responses: (i) a negative effect on body weight, except for the dose of 100 mg/kg/day in both sexes; (ii) an increase in the percentage of animals that responded to the thermal stimulus above the defined cut-off time interval and the response latency in both sexes; (iii) dose-specific changes within sexes in behavior provoked by a novel anxiogenic environment, i.e., in females less anxiety-like/risk-assessment behavior in response to the lowest exposure dose, and in males more pronounced anxiety-like/risk-assessment behavior after exposure to the highest dose and 100 mg/kg/day; (iv) dose- specific changes within sexes in novelty-induced psychomotor activity, i.e., in females a decrease in stereotypy-like activity along with an increase in Frontiers in Behavioral Neuroscience 01 frontiersin.org