Date of Award


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Major Professor

Christopher Harshaw


Epidemiological studies reported associations between early-life exposure Acetaminophen (APAP) exposure and increased risk of Autism Spectrum Disorder (ASD). Rodent studies parallel epidemiological reports, with APAP-exposed animals showing more abnormal social and increased repetitive behaviors. However, mechanisms underlying sex-specific behavioral responses to APAP remain unclear. Here, a rat model was developed to examine possible interactions between APAP and early-life hormonal milieus during the neonatal period of brain sexual differentiation. Subcutaneous (s.c.) injections of either 17�-Estradiol (E2; masculinized) or Letrozole (LTZ; feminized) were administered from Postnatal Days (PD) 1-11 followed by either APAP or saline 45 min after the first injection on PD 5, 8, and 11. Behavioral assays of play, social conditioned place preference, mate preference, and motor/anxiety behaviors were assessed. Results revealed interactions between sex, APAP, and E2 (and LTZ) on all behavioral outcomes. These results indicate that APAP may produce sex-specific behavioral responses by interacting with early-life hormonal milieus.


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Available for download on Saturday, May 27, 2023