PMID- 24361869
OWN - NLM
STAT- MEDLINE
DCOM- 20141014
LR  - 20220408
IS  - 1096-0929 (Electronic)
IS  - 1096-0929 (Linking)
VI  - 138
IP  - 1
DP  - 2014 Mar
TI  - Paracetamol (acetaminophen) administration during neonatal brain development 
      affects cognitive function and alters its analgesic and anxiolytic response in 
      adult male mice.
PG  - 139-47
LID - 10.1093/toxsci/kft329 [doi]
AB  - 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 x 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 x 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.
FAU - Viberg, Henrik
AU  - Viberg H
AD  - * Department of Environmental Toxicology.
FAU - Eriksson, Per
AU  - Eriksson P
FAU - Gordh, Torsten
AU  - Gordh T
FAU - Fredriksson, Anders
AU  - Fredriksson A
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20131221
PL  - United States
TA  - Toxicol Sci
JT  - Toxicological sciences : an official journal of the Society of Toxicology
JID - 9805461
RN  - 0 (Analgesics, Non-Narcotic)
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 362O9ITL9D (Acetaminophen)
SB  - IM
MH  - Acetaminophen/pharmacokinetics/*toxicity
MH  - Analgesics, Non-Narcotic/pharmacokinetics/*toxicity
MH  - Animals
MH  - Animals, Newborn
MH  - Anxiety/*chemically induced/metabolism
MH  - Behavior, Animal/*drug effects
MH  - Brain/*drug effects/growth & development/metabolism
MH  - Brain-Derived Neurotrophic Factor/metabolism
MH  - Chromatography, High Pressure Liquid
MH  - Cognition Disorders/*chemically induced
MH  - Enzyme-Linked Immunosorbent Assay
MH  - Male
MH  - Maze Learning/drug effects
MH  - Mice
MH  - Motor Activity/drug effects
MH  - Nociception/drug effects
MH  - Spatial Behavior/drug effects
OTO - NOTNLM
OT  - behavior
OT  - developmental neurotoxicity
OT  - neonatal
OT  - paracetamol (acetaminophen).
EDAT- 2013/12/24 06:00
MHDA- 2014/10/15 06:00
CRDT- 2013/12/24 06:00
PHST- 2013/12/24 06:00 [entrez]
PHST- 2013/12/24 06:00 [pubmed]
PHST- 2014/10/15 06:00 [medline]
AID - kft329 [pii]
AID - 10.1093/toxsci/kft329 [doi]
PST - ppublish
SO  - Toxicol Sci. 2014 Mar;138(1):139-47. doi: 10.1093/toxsci/kft329. Epub 2013 Dec 
      21.