Behavioral data file following treatment of laboratory rats with paracetamol

Based on several lines of evidence, numerous investigators have suggested
that acetaminophen exposure during early development can induce
neurological disorders. We had previously postulated that acetaminophen
exposure early in life, if combined with antioxidants that prevent
accumulation of NAPQI, the toxic metabolite of acetaminophen, might be
innocuous. In this study, we administered acetaminophen at or below the
currently recommended therapeutic dose to male laboratory rat pups aged
4-10 days. The antioxidants cysteine and mannitol were included to prevent
accumulation of NAPQI. In addition, animals were exposed to a cassette of
common stress factors: an inflammatory diet, psychological stress,
antibiotics, and mock infections using killed bacteria. At age 37-49 days,
observation during introduction to a novel conspecific revealed increased
rearing behavior, an asocial activity, in animals treated with
acetaminophen plus antioxidants, regardless of their exposure to oxidative
stress factors (2-way ANOVA; P < 0.0001). This observation would
suggest that the initial hypothesis is incorrect, and that oxidative
stress mediators do not entirely eliminate the effects of acetaminophen on
neurodevelopment. This study provides additional cause for caution when
considering the use of acetaminophen in the pediatric population, and
provides evidence that the effects of acetaminophen on neurodevelopment
need to be considered both in the presence and in the absence of oxidative
stress.