# Effect of prenatal exposure to acetaminophen during critical period of brain growth spurt on exploratory and cognitive behavior: Guinea pig model

> **NIH NIH R21** · UNIVERSITY OF MARYLAND BALTIMORE · 2020 · $231,750

## Abstract

ABSTRACT
Recommended doses of the analgesic acetaminophen (N-acetyl-p-aminophenol; Tylenol®, APAP) were
presumed to be safe for pregnant women until epidemiological studies reported that children prenatally
exposed to APAP are at high risk of developing a number of neurological disorders, including attention-
deficit/hyperactivity disorder (ADHD) and autism spectrum disorder (ASD). It is important to note, however, that
these studies did not establish a cause-consequence relationship between prenatal APAP exposure and
childhood neurological disorders. Preclinical studies, on the other hand, have shown that exposure of mice and
rats to APAP during their neonatal period of brain growth spurt causes cognitive deficits among other
neurobehavioral impairments in early adulthood. Unfortunately, the temporal development of the human brain
does not parallel that of the mouse or the rat brain. Therefore, the question as to whether gestational exposure
to APAP causes disruption of fetal brain development and, thereby, compromises neurobehavioral functions
later in life remains unanswered. Here, we propose to use the guinea pig as the animal model of choice to
test the central hypothesis that prenatal exposure to APAP during the period of brain growth spurt has
long-term, sex-dependent effects on emotional and cognitive behavior that correlate with disruption of
the electrical activity and/or structural integrity of the brain. The guinea pig is a unique animal model,
because its placental structure, the temporal course of its brain development, and APAP metabolism during
pregnancy closely resemble those of humans. A multidisciplinary approach involving behavioral assays,
electroencephalography (EEG), and immunohistochemistry (IHC), and a placebo-controlled, randomized, blind
design that minimizes experimental bias and maximizes scientific rigor will be used to address two specific
aims. In Aim 1, experiments will determine whether male and female offspring born from guinea pigs orally
treated with APAP (50-100 mg/kg twice a day for 10 days) during the gestational critical period of fetal brain
growth spurt present impaired exploratory, social, and/or cognitive behavior. These are behavioral domains
impaired in neurological disorders associated with prenatal APAP exposure of children. At the end of the
behavioral test, animals will be used in the experiments designed in Aim 2 to determine whether the prenatal
exposure to APAP causes significant alterations of the electrical brain activity, measured in telemetric EEG,
and/or disruption of the structural integrity of the hippocampus, a brain region critical known to be structurally
disrupted in ADHD and ASD. This approach will enable us to identify functional and structural correlates of the
behavioral outcomes in APAP-exposed offspring. Successful completion of this study will fill in the
knowledge gap regarding the safety of gestational use of APAP. It will also lay the groundwork for
future studies aimed at...

## Key facts

- **NIH application ID:** 9892621
- **Project number:** 1R21HD095429-01A1
- **Recipient organization:** UNIVERSITY OF MARYLAND BALTIMORE
- **Principal Investigator:** Jacek A. Mamczarz
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $231,750
- **Award type:** 1
- **Project period:** 2020-09-01 → 2022-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9892621

## Citation

> US National Institutes of Health, RePORTER application 9892621, Effect of prenatal exposure to acetaminophen during critical period of brain growth spurt on exploratory and cognitive behavior: Guinea pig model (1R21HD095429-01A1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/9892621. Licensed CC0.

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