Polyethylene Glycol 3350 Does Not Lead to Behavior Changes in Animal ModelPolyethylene Glycol 3350 Does Not Lead to Behavior Changes in Animal Model https://pediatricsnationwide.org/wp-content/uploads/2021/12/012219bt2287-1024x683.jpg 1024 683 Mary Bates, PhD Mary Bates, PhD https://secure.gravatar.com/avatar/c6233ca2b7754ab7c4c820e14eb518c8?s=96&d=mm&r=g
- December 22, 2021
- Mary Bates, PhD
The laxative affected stool consistency and gut bacteria but did not alter anxiety-like behavior in mice.
Polyethylene glycol 3350 (PEG3350) is a laxative commonly used to treat constipation in children. Over the years, the Food and Drug Administration has received some reports of neuropsychiatric symptoms in children administered PEG3350, including anxiety, aggression and obsessive-compulsive behaviors. Since neuropsychiatric and behavioral disorders are prevalent in children with constipation, it has been challenging to determine whether such adverse behavioral effects are due to the medication or associated with a pre-existing condition.
Ross Maltz, MD, (pictured above) a pediatric gastroenterologist at Nationwide Children’s, set out with his colleagues to study this question in mice. The results were reported recently in the Journal of Pediatric Gastroenterology and Nutrition.
In the first experiment, mice were administered either a high or a low dose of PEG3350 daily for two weeks. Additional mice were given a high or low dose of an alternative laxative (magnesium citrate) or water. The researchers assessed anxiety-like behaviors using several standardized tests before treatment, after two weeks of treatment, and after a two-week washout period.
“We compared the groups and didn’t see any differences in anxiety-like behavior in any of the mice,” says Dr. Maltz, who is also an assistant professor of clinical pediatrics at The Ohio State University College of Medicine. “But with repeated exposure to the behavioral tests, mice can get habituated and respond less over time. So we did another experiment.”
The team’s second experiment used the same design but the mice only underwent behavioral testing once, at the end of the two-week treatment period. Again, they found that administration of PEG3350 did not alter anxiety-like behaviors.
Dr. Maltz and his colleagues also investigated the composition of the gut microbiome in the mice, as a possible mechanistic explanation should behavioral effects have been found. The researchers found that the relative abundances of a number of bacterial taxa were significantly altered in mice treated with PEG3350, especially the high dose.
“Although we saw changes in the gut microbiome and stool consistency (indicating the laxative was efficacious), we did not see any anxiety-like behaviors in these mice,” says Dr. Maltz.
Although this study found no evidence that PEG3350 (or magnesium citrate) alters anxiety-like behavior in mice, Dr. Maltz says there are still questions for further studies. For instance, this study could be replicated with different behavioral tests to probe potential changes in aggression or obsessive-compulsive behaviors, or even different aspects of anxiety-like behavior. In addition, Dr. Maltz cautions that this was done in an animal model, and further evaluations in pediatric patients could be conducted.
“My colleagues and I feel that PEG3350 is safe and effective medication for patients with chronic constipation,” says Dr. Maltz. “We still use it, first-line, to treat constipation.
“There are alternative choices, but I have no reservations using PEG3350 in patients or even for myself or family members, if warranted.”
Salman SS, Williams KC, Marte-Ortiz P, Rumpf W, Mashburn-Warren L, Lauber CL, Bailey MT, Maltz RM. Polyethylene glycol 3350 changes stool consistency and the microbiome but not behavior of CD1 mice. Journal of Pediatric Gastroenterology and Nutrition. 2021 Oct 1;73(4):499-506. doi: 10.1097/MPG.0000000000003222.
Image credit: Nationwide Children’s
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