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Paracetamol (acetaminophen) administration during neonatal brain development affects cognitive function and alters its analgesic and anxiolytic response in adult male mice
Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Organismal Biology, Environmental toxicology.
Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Organismal Biology, Environmental toxicology.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care. (Pain Research)
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Psychiatry, University Hospital.
2014 (English)In: Toxicological Sciences, ISSN 1096-6080, E-ISSN 1096-0929, Vol. 138, no 1, 139-147 p.Article in journal (Refereed) Published
Abstract [en]

Background:

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.

Objectives:

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.

Methods:

10-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, 4 hours apart). Concentrations of paracetamol and BDNF were measured in the neonatal brain and behavioral testing was done when animals reached adulthood.

Results:

The present study shows that neonatal exposure of mice to paracetamol, single dose 30 mg/kg body weight) or repeated doses (30+30 mg/kg body weight), increase the levels of BDNF in the neonatal brain and can cause behavioral disturbances in the young adult animal, including lack of habituation to a novel home environment, hyperactivity, and decreased learning and memory capability. Another consequence is that the analgesic and anti-anxiolytic effects of paracetamol treatment, in the adult mice, were diminished.

Conclusions:

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.

Place, publisher, year, edition, pages
2014. Vol. 138, no 1, 139-147 p.
National Category
Medical and Health Sciences
Identifiers
URN: urn:nbn:se:uu:diva-215810DOI: 10.1093/toxsci/kft329ISI: 000332045500013PubMedID: 24361869OAI: oai:DiVA.org:uu-215810DiVA: diva2:688540
Available from: 2014-01-17 Created: 2014-01-17 Last updated: 2017-12-06Bibliographically approved

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Viberg, HenrikEriksson, PerGordh, TorstenFredriksson, Anders

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