López-Escobar, BeatrizFernández-Torres, RutVargas-López, VivianaVillar-Navarro, MercedesRybkina, TatyanaRivas-Infante, EloyHernández-Viñas, AyleenÁlvarez Del Vayo, ConcepciónCaro-Vega, JoséSánchez-Alcázar, José A.González-Meneses, AntonioCarrión, M. ÁngelYbot-González, Patricia2022-06-282022-06-282020-05-06López-Escobar B, Fernández-Torres R, Vargas-López V, Villar-Navarro M, Rybkina T, Rivas-Infante E, et al. Lacosamide intake during pregnancy increases the incidence of foetal malformations and symptoms associated with schizophrenia in the offspring of mice. Sci Rep. 2020 May 6;10(1):7615http://hdl.handle.net/10668/3717The use of first and second generation antiepileptic drugs during pregnancy doubles the risk of major congenital malformations and other teratogenic defects. Lacosamide (LCM) is a third-generation antiepileptic drug that interacts with collapsing response mediator protein 2, a protein that has been associated with neurodevelopmental diseases like schizophrenia. The aim of this study was to test the potential teratogenic effects of LCM on developing embryos and its effects on behavioural/histological alterations in adult mice. We administered LCM to pregnant mice, assessing its presence, and that of related compounds, in the mothers' serum and in embryonic tissues using liquid chromatography coupled to quadrupole/time of flight mass spectrometry detection. Embryo morphology was evaluated, and immunohistochemistry was performed on adult offspring. Behavioural studies were carried out during the first two postnatal weeks and on adult mice. We found a high incidence of embryonic lethality and malformations in mice exposed to LCM during embryonic development. Neonatal mice born to dams treated with LCM during gestation displayed clear psychomotor delay and behavioural and morphological alterations in the prefrontal cortex, hippocampus and amygdala that were associated with behaviours associated with schizophrenia spectrum disorders in adulthood. We conclude that LCM and its metabolites may have teratogenic effects on the developing embryos, reflected in embryonic lethality and malformations, as well as behavioural and histological alterations in adult mice that resemble those presented by patients with schizophrenia.enAtribución 4.0 Internacionalhttp://creativecommons.org/licenses/by/4.0/LacosamideAnimalesMiceFetusDose-response relationship, drugMemoryPregnancySchizophreniaMalformationsLacosamidaAnimalesRatonesFetoRelación dosis-respuesta a drogaMemoriaEmbarazoEsquizofreniaAnomalías congénitasEfectos tardíos de la exposición prenatalMedical Subject Headings::Organisms::Eukaryota::AnimalsMedical Subject Headings::Phenomena and Processes::Physiological Phenomena::Pharmacological Phenomena::Dose-Response Relationship, DrugMedical Subject Headings::Check Tags::FemaleMedical Subject Headings::Anatomy::Embryonic Structures::FetusMedical Subject Headings::Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Data Collection::Vital Statistics::Morbidity::IncidenceMedical Subject Headings::Phenomena and Processes::Musculoskeletal and Neural Physiological Phenomena::Musculoskeletal Physiological Phenomena::Musculoskeletal Physiological Processes::Movement::LocomotionMedical Subject Headings::Psychiatry and Psychology::Psychological Phenomena and Processes::Mental Processes::Learning::MemoryMedical Subject Headings::Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Rodentia::Muridae::Murinae::MiceMedical Subject Headings::Phenomena and Processes::Reproductive and Urinary Physiological Phenomena::Reproductive Physiological Phenomena::Reproductive Physiological Processes::Reproduction::PregnancyMedical Subject Headings::Diseases::Female Urogenital Diseases and Pregnancy Complications::Pregnancy Complications::Prenatal Injuries::Prenatal Exposure Delayed EffectsMedical Subject Headings::Psychiatry and Psychology::Mental Disorders::Schizophrenia and Disorders with Psychotic Features::SchizophreniaMedical Subject Headings::Chemicals and Drugs::Chemical Actions and Uses::Pharmacologic Actions::Therapeutic Uses::Central Nervous System Agents::Anticonvulsantsresearch article32376856open access10.1038/s41598-020-64626-92045-2322PMC7203245