Development of [3H]nicotine binding sites in brain regions of rats exposed to nicotine prenatally via maternal injections or infusions.
The fetal and postnatal development of binding sites for [3H]nicotine was examined in brain regions of normal rats and rats whose mothers received nicotine injections or infusions, starting before fetal implantation (gestational day 4) and continuing to gestational day 20. The normal ontogenetic pattern of binding indicated a small but detectable concentration of sites during late gestation, and a substantial increase after birth, primarily during the period in which the majority of cholinergic synapses is forming. The adult pattern of regional selectivity of binding capabilities, namely midbrain + brainstem greater than cerebral cortex much greater than cerebellum, was not present at birth, but rather developed over the ensuing 3 weeks postpartum. Fetal exposure to nicotine produced an elevation in binding detectable during the course of drug exposure (gestational day 18), a finding similar to nicotine's effects in mature brain. However, examination of the subsequent developmental pattern of [3H]nicotine binding indicated a generalized disruption of receptor acquisition, in that alterations persisted far beyond the period in which drug exposure was terminated. The greatest effect was seen in a region relatively poor in receptor sites (cerebellum), and a larger stimulation was obtained with injected vs. infused nicotine. Because the cerebellum is the primary target for disruption of cellular development by prenatal nicotine exposure, these results are consistent with a primary teratologic action of the drug rather than direct effects on development of [3H]nicotine receptors.
Slotkin, TA; Orband-Miller, L; Queen, KL
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