Efeitos da exposição à nicotina e à fumaça de cigarro durante a lactação sobre o sistema de recompensa cerebral em ratos

Abstract

Children from smoking mothers are more susceptible to become obese adults and to become drug or food addicts. Drugs and food activate the mesolimbic reward pathway, causing a sense of pleasure that induces further consumption.Thus, we studied the relationship between only nicotine or tobacco smoke exposure during lactation with feeding behavior and brain dopaminergic reward system at adulthood, in two programming models: Model I, on the postnatal day (PN) 2, lactating rats were implanted with minipumps releasing nicotine (NIC) or saline (C) for 14 days. On PN150 and again on PN160, offspring were divided into 4 groups for a food challenge: N-SC and C-SC received standard chow; N-SSD and C-SSD could freely select between hyperlipidic and hyperglicidic diets. Mothers were euthanized only in 21ª of lactation and offspring were euthanized in PN15 (with nicotine), PN21 and PN170 (withdraw). At weaning (PN21), NIC dams had: lower tyrosine hydroxylase (TH), higher OBRb and SOCS3 contents in ventral tegmental area (VTA); lower TH, higher dopamine receptor 1 (D1R), dopamine receptor 2 (D2R) and dopamine transporter (DAT) contents in nucleus accumbens (NAc); higher TH content in dorsal striatum (DS); and higher D2R and SOCS3 contents in arcuate nucleus (ARC). On PN15, NIC pups had higher D1R, D2R and lower DAT contents in NAc, while on PN21 they had lower DAT in DS, and lower pSTAT3 content in ARC. On PN170, SSD animals showed an increased food intake compared with SC ones and a preference for the hyperlipidic chow. However, N-SSD animals consumed relatively more hyperglicidic chow than C-SSD ones. N offspring presented lower D2R and DAT contents in the NAc, and lower D2R in the ARC. Model II, nursing rats and their pups were divided into: tobacco smoke-exposed (S group: 4 times/day, from the 3rd to the 21th day of lactation), and ambient air-exposed (C group). On PN175, offspring were divided into 4 groups for a food challenge: S-SC and C-SC received standard chow; S-SSD and C-SSD could select between hyperlipidic and hyperglicidic diets. Food intake was recorded after 30 min and 12 h. On PN180, offspring were euthanized. SSD animals presented a higher food intake compared with SC ones. S-SSD animals ate more than C-SSD ones at 30 min and 12 h. Both groups preferred the hyperlipidic chow. However, S-SSD animals consumed relatively more hyperlipidic chow than C-SSD at 30 min. S animals presented lower TH content in the ventral tegmental area, lower TH, D2R, higher D1R contents in the NAc and lower OBRb in the ARC. We showed that both nicotine alone as well as cigarette smoke exposure during the lactation resulted in changes in the dopaminergic system of the offspring, programming the eating behavior due to decreased dopamine in the NAc.