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. 2025 Sep;62(9):12164-12183.
doi: 10.1007/s12035-025-05004-2. Epub 2025 May 16.

Ontogenic, Immunological, and Behavioral Changes of Crack Cocaine Exposure During the Gestational Period

Yngrid Mickaelli Oliveira Dos Santos #  1 , Igor Santana-Melo #  2 , Amanda Larissa Dias Pacheco  1 , Milenna Maria Jatoba Hasten Reiter  1 , Maisa de Araújo Costa  1 , Keyla Silva Nobre Pires  1 , Fernanda Maria Araújo de Souza  1 , Jucilene Freitas-Santos  1 , Mayara Rodrigues Barbosa  1 , Jeferson Santana Ursulino  3 , Marvin Paulo Lins  1   4   5 , Rayssa Gabriely Duarte Torres  1 , Amanda de Barros Coutinho  1 , Eloisa Bortolote Oliosi  1 , Bianca Rodrigues Melo da Silva  1 , Keylla Lavínia da Silva Oliveira  1 , Daniel Leite Goes Gitai  1 , Ana Catarina Rezende Leite  3 , Thiago Mendonça de Aquino  3 , Marcelo Duzzioni  1 , Alexandre Urban Borbely  1 , Olagide Wagner de Castro  6
Affiliations

Ontogenic, Immunological, and Behavioral Changes of Crack Cocaine Exposure During the Gestational Period

Yngrid Mickaelli Oliveira Dos Santos et al. Mol Neurobiol. 2025 Sep.

Abstract

Crack cocaine has a high addictive power that stimulates the central nervous system (CNS), and its high consumption by women of reproductive age has generated many challenges for public health. Crack cocaine use by pregnant women has been correlated with CNS malformations, cell damage, and changes in the immune system. Our purpose was to evaluate the effects of gestational exposure to crack cocaine in pregnant rats on ectoplacental cone cells, immune organs, maternal behavior, anxiety-like phenotype, metabolites, and sensorimotor reflex development of offspring. Pregnant rats were exposed to air or crack cocaine (200 mg) from the 5th gestational day (5thGD) to the 9th GD or until the end of pregnancy. Our findings showed that gestational exposure to crack cocaine increased trophoblast cell death, associated with reduced ectoplacental cone outgrowth in vitro. Furthermore, anxiogenic-like behavior in pregnant rats and negligence in maternal care were observed after exposure to crack cocaine. The development of motor reflexes in the offspring remained unchanged. In addition, exposure to crack cocaine during pregnancy reduced the relative weight of the spleen and CD8 + T lymphocyte subsets. No changes were observed in the thymus. Finally, we observed a series of changes in the metabolites of lactating rats exposed to crack cocaine during pregnancy. Taken together, our findings provide new insight into gestational changes promoted following exposure to crack cocaine and support future clinical interventions and treatments.

Keywords: Lymphoid organ; Metabolomics; Placenta. Maternal-infant bonding; Substance of abuse.

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Conflict of interest statement

Declarations. Ethics Approval: All applicable international, national, and/or institutional guidelines for the care and use of animals were followed. Experiments were performed in accordance with the NIH guidelines for the care and use of laboratory animals, and with approval of the Federal University of Alagoas Animal Use Ethics Committee (Protocol #28/2021). Consent to Participate: Not applicable. Consent to Publish: Not applicable. Competing Interests: The authors declare no competing interests.

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