Neurobehavioral teratogenic effects of thalidomide in rats

Thalidomide-induced embryopathy has been known for four decades, however, the drug has been reintroduced for human use in a number of countries, including the United States. In utero thalidomide exposure in humans is associated with central nervous system (CNS) effects in addition to the well-known limb, ear and other malformations. Despite knowledge of these CNS effects,, not a single experimental study could be found that examined thalidomide for possible developmental neurobehavioral effects. In the present experiment, gravid Sprague-Dawley rats were treated with either thalidomide (100 mg/kg by gavage) or vehicle (propylene glycol) on embryonic days E7-18 and allowed to deliver and raise their own offspring. The offspring were evaluated in a series of neurobehavioral tests (reflexes, locomotor activity, startle reactivity and learning in the Morris and Cincinnati water mazes). There was a small reduction in maternal weight among thalidomide-treated dams during midgestation. Thalidomide offspring showed increased preweaning mortality and male-specific, late onset reduction in growth that persisted until the end of the study. Male thalidomide offspring showed significant increases in errors and latency in the multiple-T Cincinnati water maze. Although rats are refractory to thalidomide-induced teratogenesis, the present results suggest that thalidomide selectively impairs offspring survival and growth and at least one type of learning among male offspring. (C) 2001 Elsevier Science Inc. All rights reserved.