Neurobehavioral teratogenic effects of thalidomide in rats

• Published in: Neurotoxicology and teratology 2001-05, Vol.23 (3), p.255-264
• Main Authors: Vorhees, Charles V, Weisenburger, Walter P, Minck, Daniel R
• Format: Article
• Language: English
• Subjects: Animals; Behavior, Animal - drug effects; Biological and medical sciences; Body Weight - drug effects; Cincinnati water maze; Developmental neurotoxicity; Drug toxicity and drugs side effects treatment; Female; Male; Maze Learning - drug effects; Medical sciences; Miscellaneous (drug allergy, mutagens, teratogens...); Morris water maze; Motor Activity - drug effects; Neurotoxicity Syndromes - pathology; Neurotoxicity Syndromes - psychology; Orientation - drug effects; Pharmacology. Drug treatments; Postural Balance - drug effects; Pregnancy; Prenatal effects; Rats; Rats, Sprague-Dawley; Reflex, Startle - drug effects; Smell - drug effects; Sprague–Dawley rats; Swimming - physiology; Teratogens - toxicity; Thalidomide; Thalidomide - toxicity
• ISSN: 0892-0362; 1872-9738
• DOI: 10.1016/S0892-0362(01)00140-4

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.