Resumo

The Word Health Organization estimates that there are approximately 250 million women smokers in the world. In developing countries, the prevalence of smoking varies from 11% to 35% in pregnant women, constituting a public health concern. Nicotine, a cholinergic agonist that is considered one the main active components of cigarette smoke, causes deleterious effects on brain development, however, most studies investigate its effects during rodents’ gestation, which corresponds to the first two trimesters of human gestation. In the present study, we focused on nicotine effects on the brain cholinergic system during the third trimester equivalent of human gestation. Lactating rats were exposed either to nicotine (NIC, 6 mg/Kg/day) or to saline (SAL) via osmotic minipumps (s.c.) from the 2nd to the 16th postnatal day (PN). NIC and SAL offspring were sacrificed during exposure (PN15, n=42) or at short (PN30, n=16) or long term withdrawal (PN90, n=19). Four cholinergic biomarkers were considered. For evaluation of effects on nicotinic acetylcholine receptors (nAChRs), we utilized [3H]cytisine, a ligand that binds selectively to the a4b2 nAChR. We also assessed the binding of [3H]hemicholinium-3 (HC-3) to the high-affinity presynaptic choline transporter, choline acetyltransferase (ChAT) and acetylcholinesterase (AChE) activities in the cerebral cortex of the offspring. NIC offspring presented nAChR upregulation (p=0.048) during exposure that was reversed at short term withdrawal. Interestingly, a significant nAChR downregulation was observed at long term withdrawal (p=0.006). Nicotine reduced HC-3 binding during exposure (p=0.048). This effect was maintained at short term withdrawal (p=0.003) but disappeared at long term withdrawal. There were no effects for ChAT and AChE. These data indicate that maternal nicotine exposure during the third trimester equivalent of human gestation promotes cholinergic system alterations in the offspring’s cerebral cortex. In addition, our data indicate that detrimental effects are observable even long after the exposure has been interrupted.