Benzodiazepines and the developing rat: A critical review

Abstract

This paper reviews: (1) the development of benzodiazepine binding-sites and the GABA system; (2) the evidence that prenatal exposure to benzodiazepines can cause malformations; (3) other persisting effects of developmental exposure to benzodiazepines; and (4) the behavioral effects of benzodiazepines (and other relevant drugs) in immature animals. The review concentrates on the rat, since fundamental work in other species is scarce. The data on neurochemical development are found to be generally consistent; however, reports that the enhancement of benzodiazepine binding by GABA varies with age are controversial. The physical development of the rat is disturbed only by extremely high doses of benzodiazepines. The evidence for persisting effects after early exposure to benzodiazepines is impressive at first sight, but in most studies, confounding variables have not been eliminated. Startle and some learning tasks are affected by prenatal diazepam; submissiveness is affected by neonatal lorazepam; social behaviour and convulsions are affected by neonatal CGS 8216. Benzodiazepines inhibit chemically-induced seizures in neonatal rats, but the developmental profile of sensitivity to the convulsants is disputed. Benzodiazepines stimulate motor behavior in the neonatal rat.