PRENATAL NICOTINE ALTERS NICOTINIC RECEPTOR DEVELOPMENT IN THE MOUSE-BRAIN

Maternal smoking during pregnancy may affect development of the child, but little is known about potential mechanisms of these effects. Sinc e chronic nicotine treatment alters brain nicotinic receptors in adult s and also evokes tolerance which is regulated by genetic factors, pre gnant mice of two inbred strains underwent chronic nicotine infusion t o determine whether the developmental pattern of mouse brain nicotinic receptors would be altered. C3H/2ibg and C57BL/6ibg mice were infused SC with saline or 2.0 mg/kg/h nicotine during the last half of pregna ncy. The developmental profiles of [H-3]nicotine and alpha-[I-125]bung arotoxin binding in seven brain regions obtained from the offspring we re measured. Prenatal nicotine treatment increased levels of [H-3]nico tine binding at birth in the C3H hypothalamus, hippocampus, and possib ly the cortex, and in the C57BL cortex. At later ages (20-30 days), [H -3]nicotine binding was elevated in the C3H hindbrain, hippocampus, st riatum, midbrain, and possibly the cortex. The C57BL hindbrain, hippoc ampus, midbrain, and cortex also showed increased binding at 20-30 day s. Little, if any, effect of prenatal nicotine treatment was observed on the development of the alpha-[I-125]bungarotoxin binding site. Sinc e upregulated [H-3]nicotine binding returns to control levels in adult animals within seven days following termination of chronic nicotine i nfusion, it is unlikely that simple upregulation is responsible for th e changes observed in 20-30-day-old mouse brains.