ABSTRACT
Nicotine exposure causes the release of dopamine from the ventral tegmental area (VTA) to the nucleus accumbens (NAc). We have previously shown that maternal exposure to nicotine during lactation causes hyperleptinemia in dams and pups, and leptin is known to decrease dopamine release from the VTA. Here we evaluated whether maternal exposure to nicotine during lactation causes changes in dopamine and leptin signaling pathways at the end of exposure and after 5days of withdrawal in the: VTA, NAc, arcuate nucleus (ARC) and dorsal striatum (DS). On postnatal day (PN) 2, lactating Wistar rats were implanted with minipumps releasing nicotine (NIC; 6mg/kg/day, s.c.) or saline (C) for 14days. Offspring were tested in the elevated plus maze (EPM) and open field on PN14 or PN20, and euthanized on PN15 or PN21. Entries into the open arms and head dips in the EPM were reduced in NIC pups at P20. At weaning (PN21), NIC dams had: lower tyrosine hydroxylase (TH), higher OBRb and SOCS3 contents in VTA; lower TH, higher D1R, D2R and DAT contents in NAc; higher TH content in DS; and higher D2R and SOCS3 contents in ARC. On PN15, NIC offspring 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. We evidenced that postnatal nicotine exposure induces relevant changes in the brain reward system of dams and pups, possibly associated with changes in leptinemia and increased offspring anxiety-like behavior.
Subject(s)
Lactation , Neural Pathways/drug effects , Nicotine/pharmacology , Receptors, Dopamine D1/metabolism , Receptors, Dopamine D2/metabolism , Animals , Arcuate Nucleus of Hypothalamus/drug effects , Arcuate Nucleus of Hypothalamus/metabolism , Corpus Striatum/drug effects , Corpus Striatum/metabolism , Female , Male , Maternal Exposure , Maze Learning/drug effects , Motor Activity/drug effects , Nucleus Accumbens/drug effects , Nucleus Accumbens/metabolism , Rats , Ventral Tegmental Area/drug effects , Ventral Tegmental Area/metabolismABSTRACT
The mesolimbic reward pathway is activated by drugs of abuse and palatable food, causing a sense of pleasure, which promotes further consumption of these substances. Children whose parents smoke are more vulnerable to present addictive-like behavior to drugs and food.We evaluated the association between maternal nicotine exposure during lactation with changes in feeding, behavior and in the dopaminergic reward system. On postnatal day (PN) 2,Wistar rat dams were implanted with minipumps releasing nicotine (N; 6 mg/kg/day, s.c.) or saline (C) for 14 days. On PN150 and PN160, offspring were divided into 4 groups for a food challenge: N and C that received standard chow(SC); and N and C that could freely self-select (SSD) between high-fat and high-sugar diets (HFD and HSD, respectively). Offspring were tested in the elevated plus maze (EPM) and open field (OF) arena on PN152153. On PN170, offspring were euthanized for central dopaminergic analysis. SSD animals showed an increased food intake compared to SC ones and a preference for HFD. However, N-SSD animals consumed relatively more HSD than C-SSD ones. Regarding behavior, N animals showed an increase in the time spent in the EPM center and a reduction in relative activity in the OF center. N offspring presented lower dopamine receptor (D2R) and transporter (DAT) contents in the nucleus accumbens, and lower D2R in the arcuate nucleus. Postnatal exposure to nicotine increases preference for sugar and anxiety levels in the adult progeny possibly due to a decrease in dopaminergic action in the nucleus accumbens and arcuate nucleus.
Subject(s)
Anxiety/metabolism , Brain/metabolism , Dopamine/metabolism , Nicotine/toxicity , Prenatal Exposure Delayed Effects , Reward , Age Factors , Animals , Body Weight , Brain/pathology , Diet , Eating , Exploratory Behavior/physiology , Female , Food Preferences , Male , Maze Learning/physiology , Nicotinic Agonists/toxicity , Pregnancy , Prenatal Exposure Delayed Effects/chemically induced , Prenatal Exposure Delayed Effects/pathology , Prenatal Exposure Delayed Effects/physiopathology , Rats , Rats, Wistar , Receptors, Dopamine D2/metabolism , Statistics, NonparametricABSTRACT
Perinatal nutrient restriction exerts profound influences on brain development. Animals that suffer undernutrition during lactation also display impaired weight gain. Feeding behavior is mainly modulated by neural and hormonal inputs to the hypothalamus. The arcuate-paraventricular neuropeptidergic Y pathway has a prominent role in appetite regulation. The aim of this work was to study the effects of protein undernutrition during lactation on this hypothalamic pathway. We used rats from 5 to 60 postnatal (P) days whose dams were fed a 0% protein diet (PFG) or a normoprotein diet (CG) from P1 to P10. To reproduce the same amount of calorie ingested by the PFG we used an underfed group (UFG). Immunohistochemistry was performed to assess neuropeptide Y (NPY) distribution in the arcuate, periventricular and paraventricular nuclei. Our results showed a NPY immunostaining peak at P10 in all nuclei in CG animals. In UFG animals this peak was observed by P15, while, in the PFG animals only by P20. Our results suggest that the neuropeptidergic arcuate-paraventricular pathway suffered a delay in NPY distribution in undernourished animals, particularly those fed a 0% protein diet, reflecting an effect on this pathway maturation that could explain previously reported alterations on feeding behavior in these animals.
