Scientists from the University of Utah say they have discovered a new way of doing mice experiments that more sensitively and quickly reveals negative side effects from drugs being tested. In their proof-of-concept, their experiment much more pronouncedly and rapidly revealed the negative effects of the antidepressant Paxil (paroxetine) on pregnant mothers and offspring, even at relatively low doses.
The study, appearing in Neurotoxicology and Teratology, involved putting the lab mice in extremely competitive environments rather than in isolated, protected cages, the way lab mice normally live. When the mice had to battle more aggressively for territory, food, and mating opportunities, the negative effects of the Paxil appeared much more rapidly and tangibly and at much lower doses than in the original experiments with protected mice.
“Paroxetine-exposed males weighed 13% less, had 44% fewer offspring, dominated 53% fewer territories and experienced a 2.5-fold increased trend in mortality, when compared with controls,” wrote the researchers. “Paroxetine-exposed females had 65% fewer offspring early in the study, but rebounded at later time points, presumably, because they were no longer exposed to paroxetine. In cages, paroxetine-exposed breeders took 2.3 times longer to produce their first litter and pups of both sexes experienced reduced weight when compared with controls.”
These effects of Paxil were not as apparent in early trials of the drug, the researchers wrote. Low-dose paroxetine-induced health declines detected in their study “were undetected in preclinical trials with doses 2.5–8 times higher than human therapeutic doses.”
‘Darwinian’ Test Uncovers an Antidepressant’s Hidden Toxicity (University of Utah press release on Newswise, December 15, 2014)
(Abstract) Low-dose paroxetine exposure causes lifetime declines in male mouse body weight, reproduction and competitive ability as measured by the novel organismal performance assay (Gaukler, Shannon M. et al. Neurotoxicology and Teratology. January-February, 2015. doi:10.1016/j.ntt.2014.11.002)