Aspirin-induced psychoteratogenesis in rats as a function of embryonic age

Abstract

Gravid Wistar rats were treated with either 625 mg/kg of aspirin (acetylsalicylic acid) or vehicle alone on either gestational Day 11 or 12, and their progeny were evaluated postnatally using a standardized series of neurobehavioral tests and physical measurements. The results showed that aspirin given on Day 11 produced maternal and offspring growth deficits not seen when given on Day 12. In addition, aspirin on Day 11 reduced behavioral performance in the progeny on tests of pivoting locomotion, negative geotaxis orientation, home scent (olfactory) orientation, and swimming performance. Further analysis revealed that some of the behavioral effects of aspirin on Day 11 significantly covaried with the body weight reductions noted in this group, such as negative geotaxis, whereas other results showed only minor associations with weight, such as pivoting and swimming. Interestingly, the olfactory orientation results were more apparent after body weight differences were factored out. These data demonstrate that (1) aspirin causes marked differences both in behavior and postnatal growth with only a 24‐hr difference in embryonic age at the time of treatment; (2) behavioral tests are differentially affected by differences in body weight; and (3) behavioral tests appear to be measuring phenomena not reflected by growth, survival, or physical landmarks of development and, as such, add significant information about the toxicological effects of aspirin.