Prenatal nicotine exposure is associated with an increase in [125I]epibatidine binding in discrete cortical regions in rats.
Previously, it was reported that hyperactive male offspring of dams exposed to nicotine (6 mg/kg/day) during gestation had an increase in cortical alpha4-beta2 nicotinic receptor subtype density as determined by [3H]cytisine binding in tissue homogenate [Tizabi Y, Popke EJ, Rahman MA, Nespor SM, Grunberg NE. Hyperactivity induced by prenatal nicotine exposure is associated with an increase in cortical nicotinic receptors. Pharmacol, Biochem Behav 1997;58:141-6]. [125I]Epibatidine labels alpha4beta2 nicotinic receptors with higher affinity than [3H]cytisine. In the present study, using quantitative autoradiography, we evaluated the effects of in-utero exposure to nicotine (9 mg/kg/day) on [125I]epibatidine binding in 46 discrete brain regions of 36-day-old male offspring of Sprague-Dawley rats. This dosage of nicotine administered during pregnancy to same rats was shown to result in increased vertical activity in the male offspring [Tizabi Y, Russell LT, Nespor SM, Perry DC, Grunberg NE. Prenatal nicotine exposure: effects on locomotor activity and central [125I]alpha-BT binding in rats. Pharmacol, Biochem Behav (in press).]. Prenatal nicotine exposure resulted in increases in receptor densities of the somatosensory cortex (90%) and the visual cortex (107%) only. Moreover, these increases were restricted to cortical layer 1. Collectively, these results indicate that prenatal nicotine exposure affects specific nicotinic receptors in selective cortical regions of male offspring. These neurochemical effects may be responsible for some of the behavioral abnormalities seen in such offspring.
Tizabi
Y
Y
Department of Pharmacology, College of Medicine, Howard University, 520 W Street N.W., Washington, DC 20059, USA. ytizabi@howard.edu
Perry
D C
DC
D000818:Animals; D001345:Autoradiography; D001667:Binding, Competitive / Q000187:drug effects; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000378:metabolism*; D002540:Cerebral Cortex / Q000187:drug effects* / Q000378:metabolism; D005260:Female; D007457:Iodine Radioisotopes; D008297:Male; D009538:Nicotine / Q000494:pharmacology*; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D011725:Pyridines / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley
D019086:Bridged Bicyclo Compounds, Heterocyclic; D007457:Iodine Radioisotopes; D011725:Pyridines; D009538:Nicotine; C082748:epibatidine