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Updated: May 4, 2026
Neurobehavioral Assessments in a Mouse Model of Neonatal Hypoxic-ischemic Brain Injury
Published on: November 24, 2017
Paracetamol (acetaminophen) administration during neonatal brain development affects cognitive function and alters
Henrik Viberg1, Per Eriksson, Torsten Gordh
1* Department of Environmental Toxicology.
Insights
Neonatal exposure to paracetamol (acetaminophen) in mice can lead to lasting cognitive deficits and altered responses to the drug in adulthood. This highlights potential risks of early-life exposure during critical brain development periods.
Area of Science:
- Neuroscience
- Developmental Biology
- Pharmacology
Background:
- Paracetamol (acetaminophen) is a widely used medication for pain and fever.
- The endocannabinoid system plays a role in brain development.
- Environmental presence of paracetamol raises concerns about potential developmental impacts.
Purpose of the Study:
- To investigate the long-term effects of neonatal paracetamol exposure on brain development in mice.
- To assess if early paracetamol exposure causes adult behavioral and cognitive deficits.
- To determine if neonatal exposure alters the adult response to paracetamol.
Main Methods:
- Ten-day-old mice received single or repeated doses of paracetamol.
- Paracetamol and brain-derived neurotrophic factor (BDNF) levels were measured in neonatal brains.
- Adult offspring underwent behavioral testing for cognition, locomotion, and pain/anxiety responses.
Main Results:
- Neonatal paracetamol exposure (2 × 30 mg) impaired spatial learning and altered locomotor activity in adult mice.
- Adult mice exposed neonatally did not show typical paracetamol-induced pain relief or anxiety-like effects.
- Changes in BDNF levels in key brain regions were observed, potentially explaining behavioral alterations.
Conclusions:
- Acute neonatal paracetamol exposure can induce persistent cognitive deficits and modify adult drug responses.
- Early-life paracetamol exposure may disrupt critical brain development, leading to long-lasting neurodevelopmental effects.
- These findings suggest potential risks associated with paracetamol exposure during sensitive developmental windows.
Abstract:
Paracetamol (acetaminophen) is one of the most commonly used drugs for the treatment of pain and fever in children, both at home and in the clinic, and is now also found in the environment. Paracetamol is known to act on the endocannabinoid system, involved in normal development of the brain. We examined if neonatal paracetamol exposure could affect the development of the brain, manifested as adult behavior and cognitive deficits, as well as changes in the response to paracetamol. Ten-day-old mice were administered a single dose of paracetamol (30 mg/kg body weight) or repeated doses of paracetamol (30 + 30 mg/kg body weight, 4h apart). Concentrations of paracetamol and brain-derived neurotrophic factor (BDNF) were measured in the neonatal brain, and behavioral testing was done when animals reached adulthood. This study shows that acute neonatal exposure to paracetamol (2 × 30 mg) results in altered locomotor activity on exposure to a novel home cage arena and a failure to acquire spatial learning in adulthood, without affecting thermal nociceptive responding or anxiety-related behavior. However, mice neonatally exposed to paracetamol (2 × 30 mg) fail to exhibit paracetamol-induced antinociceptive and anxiogenic-like behavior in adulthood. Behavioral alterations in adulthood may, in part, be due to paracetamol-induced changes in BDNF levels in key brain regions at a critical time during development. This indicates that exposure to and presence of paracetamol during a critical period of brain development can induce long-lasting effects on cognitive function and alter the adult response to paracetamol in mice.
