Maternal dipyrone treatment during lactation in mice reduces maternal behavior and increases anxiety‐like behavior in offspring

Abstract

Dipyrone (metamizole), a powerful drug, is widely used as an analgesic and antipyretic; however, the safety of its use during lactation and the potential impact on the offspring are not well established. This study aimed to determine the effect of maternal dipyrone treatment during lactation on offspring development and emotional behavior and on the dam's maternal behavior. Hence, on postnatal day (PND) 2, drinking water only or drinking water containing dipyrone at doses of 100, 300, and 500mg/kg/day, were offered to lactating mothers up to PND9. Thereafter, all mice were provided regular drinking water. On PND2, all litters were culled to 8 pups (4 males and 4 females). Maternal behavior was evaluated at PND3, 6, 9, and 12, and at PND7 we evaluated locomotor activity in the open field. Reflex parameters and physical development of offspring were evaluated during lactation. At PND7, analysis of ultrasonic vocalization (USV) was performed. When the animals reached adolescence, we evaluated their performance in the open field, elevated plus maze (EPM), and marble burying. Our data demonstrated that maternal dipyrone treatment during lactation not only altered maternal behavior and the onset of physical and neurodevelopmental landmarks but also had an impact on anxiety-like behavior in offspring.

Cafeteria diet during the gestation period programs developmental and behavioral courses in the offspring

“…Their offspring (40 female and 40 male mice from each group) were used for the experimental procedures during adolescence (PND 30‐32). To avoid the litter effect, one couple (1 male and 1 female mouse) from each litter received an ink mark on one hind limb for observation of reflex parameters and physical development until PND 21 (n = 10 per group) (Veronesi et al, 2017). The other three couples of each litter that were not marked were used to evaluate the behavioral performance in the light dark, open field, or play behavior tests (n = 10 per group) during adolescence since each animal was used only once for a given behavioral evaluation.…”

“…The mean number of days required for the appearance of each of the above‐mentioned parameters was calculated. On PND 21, the offspring were weaned, marked with a nontoxic ink, distributed in accordance with their sex, and housed in groups of four per cage (Carvalho et al, 2016; Veronesi et al, 2017).…”

“…Activity was scored as a line crossing when a mouse removed all four paws from one square and entered another. Line crossings among the central four squares or among the peripheral eight squares of the open field were counted separately (Veronesi et al, 2017).…”

The Effects of Bisphenol A Exposure and Calbindin Knockout on Behavior, Gene Expression, and Sexual Differentiation of the Brain

“…USVs in infant rodents can be affected by genetic, pharmacological, or early-life environmental manipulations, such as chronic stress. Infant USVs during maternal separation are also correlated with anxiety-life behaviors in later life (Barua et al, 2014;Trezza et al, 2008;Veronesi et al, 2017), as was the case with gestational exposure to BPA. However, there have been no other reports on infant USVs in a BPA exposure model.…”

“…Rats selectively bred across many generations for high levels of USVs during maternal separation demonstrate significantly more anxiety and depressive-like behaviors in later life (Brunelli and Hofer, 2007;Dichter et al, 1996). Several other studies have also shown positive associations between pup USV calling and anxiety/depressive-like behaviors in adulthood (Barua et al, 2014;Trezza et al, 2008;Veronesi et al, 2017). A recent study reported that prenatal exposure to polychlorinated biphenyls (PCBs) significantly affected USVs produced by rats during affiliative interactions in adolescence and sociosexual interactions in adulthood (Bell et al, 2016).…”