title: Investigation of possible teratogenic effects in the offspring of mice exposed to methylphenidate during pregnancy.
abstract: Methylphenidate (MPH) is a central nervous system stimulant drug that increases concentration and energy level. The safety of MPH use during pregnancy is not well established. Considering the high rate of unplanned pregnancy among young women, potential for accidental exposure to MPH in early pregnancy is high. This study aimed to investigate if MPH administered during pregnancy would induce maternotoxicity, teratogenicity in mice, or both. Pregnant Swiss mice were treated with MPH (5 mg/kg, subcutaneously) or 0.9% saline (control group) from the 5th to the 17th day of pregnancy. In the MPH-treated group, a significant increase in the total number of resorptions with a consequent increase in post-implantation loss and a decrease in fetal viability were detected (all P < 0.05). A total of 91.43% of resorptions were classified as early resorptions. The group treated with MPH presented significant external (polydactyly P < 0.01), skeletal (incomplete ossification of the skull P < 0.01) and visceral (dilated ventricles P < 0.05) malformations. Behavioural effects (motor activity, memory of habituation and anxiety) were not observed in both male and female offspring evaluated at postnatal days 22, 35 and 75. The results suggest that MPH is an embryotoxic and teratogenic drug.
authors.affiliation: Department of Biology, State University of Londrina (UEL), 86051-980, Londrina, Parana, Brazil.
authors.forename: Gabriel de Araújo
authors.initials: Gde A
authors.lastname: Costa
authors.affiliation: Department of Biology, State University of Londrina (UEL), 86051-980, Londrina, Parana, Brazil.
authors.forename: Talita Cristina
authors.initials: TC
authors.lastname: Galvão
authors.affiliation: Department of Physiological Sciences, State University of Londrina (UEL), 86051-980, Londrina, Parana, Brazil.
authors.forename: André Demambre
authors.initials: AD
authors.lastname: Bacchi
authors.affiliation: Department of Physiological Sciences, State University of Londrina (UEL), 86051-980, Londrina, Parana, Brazil.
authors.forename: Estefânia Gastaldello
authors.initials: EG
authors.lastname: Moreira
authors.affiliation: Department of Biology, State University of Londrina (UEL), 86051-980, Londrina, Parana, Brazil. Electronic address: salmjs00@gmail.com.
authors.forename: Maria José Sparça
authors.initials: MJ
authors.lastname: Salles
mesh_terms: D000818:Animals; D001007:Anxiety; D001522:Behavior, Animal; D001835:Body Weight; D000697:Central Nervous System Stimulants / Q000633:toxicity*; D005260:Female; D005865:Gestational Age; D008297:Male; D018811:Maternal Exposure; D008568:Memory / Q000187:drug effects; D008774:Methylphenidate / Q000633:toxicity*; D051379:Mice; D009048:Motor Skills / Q000187:drug effects; D011247:Pregnancy; D011270:Pregnancy, Animal; D011297:Prenatal Exposure Delayed Effects / Q000139:chemically induced*; D013723:Teratogens
chemical_list: D000697:Central Nervous System Stimulants; D013723:Teratogens; D008774:Methylphenidate
keywords: behavior; methylphenidate; mice; pregnancy; teratogenicity; toxicity