Postnatal Nicotine Exposure Research Articles

The effects of pre- and post-natal nicotine exposure and genetic background on the striatum and behavioral phenotypes in the mouse

Maternal tobacco use increases the risk of complications in pregnancy and also the risk of adverse fetal outcomes. Studies have established nicotine as the principal component of tobacco smoke that leads to the majority of negative reproductive outcomes associated with maternal tobacco use. It appears the neuroteratogenicity of nicotine is mediated by complex gene-environment interactions. Genetic background contributes to individual differences in nicotine-related phenotypes. The aim of the current study was to investigate the interaction between pre- and post-natal nicotine exposure and genetic background on the histology of the striatum and behavioral measures using DBA/2J (D2) and C57BL/6J (B6) inbred mice. Alterations in neuronal cell populations, striatal brain volume, and behavior - open field (OF) activity, novel object recognition (NOR), elevated plus maze (EPM), and passive avoidance (PA) - were evaluated on post-natal day (PN) 24 and PN75. Histological data showed that pre- and post-natal nicotine exposure resulted in decreased striatal volume among preadolescent B6 and reduced neuronal number within the striatum of preadolescent B6 mice. Behavioral data showed that pre- and post-natal nicotine exposure promoted hyperactivity in D2 female mice and disrupted NOR and PA memory. Specifically, NOR deficits were significant amongst adult male mice whereas PA deficits were seen across genetic background and sex. These data suggest that nicotine treatment, genetic background, developmental stage, and sex effect striatal morphology can lead to neurobehavioral alterations.

Nicotine-induced impairments of spatial cognition and long-term potentiation in adolescent male rats

The aim of the present study was to investigate whether cognitive behavioral impairment, induced by nicotine in offspring rats, was associated with the alteration of hippocampal short-term potentiation (STP) and long-term potentiation (LTP) and to discuss the potential underlying mechanism. Young adult offspring rats were randomly divided into three groups. The groups include: control group (CC), nicotine group 1 (NC), in which their mothers received nicotine from gestational day 3 (GD3) to GD18, and nicotine group 2 (CN), in which young adult offspring rats received nicotine from postnatal day 42 (PD42) to PD56. Morris water maze (MWM) test was performed and then field excitatory postsynaptic potentials elicited by the stimulation of perforant pathway were recorded in the hippocampal dentate gyrus region. The results of the MWM test showed that learning and memory were impaired by either prenatal or postnatal nicotine exposure. In addition, it was found that there was no statistical difference of the MWM data between both nicotine treatments. In the electrophysiological test, LTP and STP were significantly inhibited in both NC and CN groups in comparison with the CC group. Notably, STP in CN group was also lower than that in the NC group. These findings suggested that both prenatal and postnatal exposure to nicotine induced learning and memory deficits, while the potential mechanism might be different from each other due to their dissimilar impairments of synaptic plasticity.

Prospective associations between early long-term household tobacco smoke exposure and antisocial behaviour in later childhood

BackgroundUsing a prospective birth cohort design, we estimate the relative contribution of long-term postnatal nicotine exposure from 17 to 86 months on children's subsequent antisocial behaviour by the end of...

Maternal Tobacco Smoke Exposure During Lactation Inhibits Catecholamine Production by Adrenal Medullae in Adult Rat Offspring

Previously, we have shown that maternal smoke exposure during lactation, even when pups are not exposed, affects biochemical profiles in the offspring at weaning, eliciting lower body adiposity, hyperinsulinemia, hypocorticosteronemia and lower adrenal catecholamine content. However, the future impact of tobacco exposure is still unknown. As postnatal nicotine exposure causes short- and long-term effects on pups' biochemistry and endocrine profiles, we have now evaluated some endocrine and metabolic parameters of the adult offspring whose mothers were tobacco exposed during lactation. For this, from day 3 to 21 of lactation, rat dams were divided in: 1) SE group, cigarette smoke-exposed (1.7 mg nicotine/cigarettes for 1 h, 4 times/day, daily), without their pups, and 2) C group, exposed to air, in the same conditions. Offspring were killed at 180-days-old. Body weight and food intake were evaluated. Blood, white adipose tissue, adrenal, and liver were collected. All significant data were p<0.05. The adult SE offspring showed no change in body weight, cumulative food intake, serum hormone profile, serum lipid profile, or triglycerides content in liver. However, in adrenal gland, adult SE offspring showed lower catecholamine content ( - 50%) and lower tyrosine hydroxylase protein expression ( - 56%). Despite the hormonal alterations during lactation, tobacco smoke exposure through breast milk only programmed the adrenal medullary function at adulthood and this dysfunction can have consequence on stress response. Thus, an environment free of smoke during lactation period is essential to improve health outcomes in adult offspring.

Neonatal nicotine exposure alters leptin signaling in the hypothalamus–pituitary–thyroid axis in the late postnatal period and adulthood in rats

Aims Postnatal nicotine exposure causes precocious primary hypothyroidism and programs for overweight, hyperleptinemia and secondary hypothyroidism in adulthood. As leptin and thyroid hormones share the ability to increase energy expenditure, we studied the effects of maternal nicotine exposure during lactation on the leptin signaling in the hypothalamus–pituitary–thyroid axis of suckling and adult offspring. Main methods Two days after delivery, osmotic minipumps were implanted in lactating rats, and nicotine (NIC, 6 mg/kg/day s.c.) or saline (C) was administered for 14 days. Offspring were killed at 15 and 180 days-old. Proteins belonging to leptin signaling were analyzed by Western blot. Significant differences had p < 0.05. Key findings In the hypothalamus, NIC offspring showed higher OB-R and pSTAT-3 content (+ 58%,+1.34x) at 15 days, and lower OB-R, JAK-2 and pSTAT-3 (−61%, −42%, −56%) at 180 days. In the pituitary gland, NIC offspring showed lower JAK-2 content (−52%) at 15 days, but no differences in adulthood. In the thyroid gland, the NIC group presented lower OB-R, JAK-2 and STAT-3 (−44%, −50%, −47%) and higher pSTAT-3 expression (+ 80%) at 15 days. At 180 days-old, NIC offspring presented higher thyroid OB-R (+ 1.54x) and lower pSTAT-3 content (−34%). Significance Neonatal primary hypothyroidism induced by maternal nicotine exposure during lactation may be partially explained by decreased leptin signaling in the thyroid, though the early stimulation of the central leptin pathway did not prevent the thyroid dysfunction. Long-term effects of postnatal nicotine exposure on leptin signaling in the hypothalamus and thyroid appear to involve central and peripheral leptin resistance in adulthood.

Late emerging effects of prenatal and early postnatal nicotine exposure on the cholinergic system and anxiety-like behavior

Animal models of prenatal nicotine exposure clearly indicate that nicotine is a neuroteratogen. Some of the persisting effects of prenatal nicotine exposure include low birth weight, behavioral changes and deficits in cognitive function, although few studies have looked for neurobehavioral and neurochemical effects that might persist throughout the lifespan. Pregnant rats were given continuous infusions of nicotine (0.96 mg/kg/day or 2.0 mg/kg/day, freebase) continuing through the third trimester equivalent, a period of rapid brain development. Because the third trimester equivalent occurs postnatally in the rat (roughly the first week of life) nicotine administration to neonate pups continued via maternal milk until postnatal day (P) 10. Exposure to nicotine during pre- and early postnatal development had an anxiogenic effect on adult rats (P75) in the elevated plus maze (EPM), and blocked extinction learning in a fear conditioning paradigm, suggesting that pre- and postnatal nicotine exposure affect anxiety-like behavior and cognitive function well into adulthood. In contrast, nicotine exposure had no effect on anxiety-like behaviors in the EPM in adolescent animals (P30). Analysis of mRNA for the α4, α7, and β2 subunits of nicotinic acetylcholine receptors revealed lower expression of these subunits in the adult hippocampus and medial prefrontal cortex following pre- and postnatal nicotine exposure, suggesting that nicotine altered the developmental trajectory of the brain. These long-term behavioral and neurochemical changes strengthen the case for discouraging cigarette smoking during pregnancy and clearly indicate that the use of the patch as a smoking cessation aid during pregnancy is not a safe alternative.

Prenatal to Early Postnatal Nicotine Exposure Impairs Central Chemoreception and Modifies Breathing Pattern in Mouse Neonates: A Probable Link to Sudden Infant Death Syndrome

Nicotine is a neuroteratogen and is the likely link between maternal cigarette smoking during pregnancy and sudden infant death syndrome (SIDS). Osmotic minipumps were implanted in 5-7 d CF1 pregnant mice to deliver nicotine bitartrate (60 mg Kg(-1) day(-1)) or saline (control) solutions for up to 28 d. Prenatal to early postnatal nicotine exposure did not modify the number of newborns per litter or their postnatal growth; however, nicotine-exposed neonates hypoventilated and had reduced responses to hypercarbia (inhalation of air enriched with 10% CO(2) for 20 min) and hypoxia (inhalation of 100% N(2) for 20 s) at postnatal days 0-3 (P0-P3). In contrast, at postnatal day 8, nicotine-exposed neonates were indistinguishable from controls. Isolated brainstem-spinal cord preparations obtained from P0 to P3 nicotine-exposed neonates showed fictive respiration with respiratory cycles longer and more irregular than those of controls, as indicated by high short- and long-term variability in Poincaré plots. In addition, their responses to acidification were reduced, indicating compromise of central chemoreception. Furthermore, the cholinergic contribution to central chemosensory responses switched from muscarinic receptor to nicotinic receptor-based mechanisms. No significant astrogliosis was detectable in the ventral respiratory group of neurons with glial fibrillary acidic protein immunohistochemistry. These results indicate that nicotine exposure affects the respiratory rhythm pattern generator and causes a decline in central chemoreception during early postnatal life. Consequently, breathing would become highly vulnerable, failing to respond to chemosensory demands. Such impairment could be related to the ventilatory abnormalities observed in SIDS.

N-methyl- d-aspartate receptor 1 changes in the piglet braintem after nicotine and/or intermittent hypercapnic-hypoxia

Prone sleeping and cigarette smoke exposure are two major risk factors for the sudden infant death syndrome (SIDS). Utilizing piglet models of early postnatal nicotine and/or intermittent hypercapnic-hypoxia (IHH) exposure, we tested the hypothesis that these exposures, separately or combined, increase N-methyl- d-aspartate (NMDA) receptor 1 (NR1) expression in the brainstem medulla. We also tested for gender-specific effects. Three piglet exposure groups were compared against 14 controls; 1, nicotine [ n=14], 2, IHH [ n=10], and 3, nicotine+IHH [ n=14], with equal gender proportions in each group. Non-radioactive in situ hybridization and immunohistochemistry were performed for NR1 mRNA and protein expression, respectively, and were quantified in seven nuclei of the brainstem medulla. NR1 mRNA was significantly increased in the gracile and inferior olivary nucleus (ION) after nicotine exposure, in five of seven nuclei after IHH exposure, and in three of seven nuclei after nicotine+IHH. The increased mRNA changes were accompanied by increased protein only in the ION after IHH and nicotine+IHH ( P=0.019, and P=0.008 respectively). By gender, control females had greater NR1 mRNA than males in the dorsal motor nucleus of vagus ( P=0.05) and for protein in the ION ( P=0.02). This gender difference was maintained after nicotine exposure in the ION with additional gender differences observed including greater mRNA in the cuneate nucleus ( P=0.04) and nucleus of the spinal trigeminal tract ( P=0.03) of males compared with females. Overall, more changes occurred at the mRNA level than protein, and IHH exposure induced more changes than nicotine or nicotine+IHH exposures. Together, these findings suggest that hypercapnic-hypoxic exposures (modeling prone sleeping or sleep apnea) are more likely to induce NMDA receptor changes in the developing brainstem than nicotine exposure alone.

Association of parental smoking behaviors and absences in school‐age children: Implications for the nurse practitioner

To examine the association between reported absences and parental smoking in school-age children, aged 6-17, and to specifically explore the impact of maternal smoking on the health and attendance of school-age children. The sample of 7488 parent-child dyads was randomly selected from the 2002 National Health Interview Survey, a multipurpose cross-sectional household interview survey conducted by the Centers for Disease Control and Prevention. The parent sample included 2673 men and 4375 women. Children's ages ranged from 6 to 17 with a mean of 11.7 years. Maternal, but not paternal, present and past smoking behavior significantly impacts the child's wellness and school attendance. The reasons for this disparity are unclear but may relate to synergistic effects of pre- and postnatal nicotine exposure, the traditional role of mother as caregiver, or specific smoking habits that increase environmental tobacco exposure. Assessment and educational strategies for families regarding the hazards of childhood exposure to environmental tobacco smoke are indicated. Specific implications for the role of the nurse practitioner across diverse specialties are addressed with emphasis on the need for development of gender, age, and culturally sensitive smoking cessation programs and support networks.

Effects of postnatal nicotine exposure on apoptotic markers in the developing piglet brain

Exposure to cigarette smoke is a risk factor for the sudden infant death syndrome (SIDS), but the ability to distinguish between the neuropathological effects of pre- versus postnatal exposure is limited in the clinical setting. To test whether postnatal nicotine exposure could contribute to the increased neuronal expression of apoptotic markers that we have previously observed in SIDS infants, as well as including study of gender influences, we developed a piglet model to mimic passive smoking in the early postnatal period. Piglets were exposed to nicotine (2 mg/kg/day infused via an implanted osmotic minipump) within 48 h of birth until the age of 13–14 days, when the brain was collected for study. Four piglet groups included: control females ( n=7), control males ( n=7), nicotine females ( n=7), and nicotine males ( n=7). Apoptotic markers included immunohistochemistry for activated caspase-3, and for DNA fragmentation or terminal deoxynucleotidyltransferase-mediated dUTP nick-end labeling (TUNEL) in seven nuclei of the brainstem caudal medulla and two subregions of the hippocampus (CA4 and dentate gyrus). Among control females compared with males, there was less active caspase-3 and less TUNEL in the dorsal motor nucleus of vagus (DMNV), and there was less TUNEL in the nucleus of the spinal trigeminal tract (NSTT). Compared with controls, nicotine-exposed male piglets had increased TUNEL staining in the cuneate nucleus ( P=0.05), and increased active caspase-3 in the hypoglossal, gracile and dentate gyrus ( P<0.05 for each). Nicotine-exposed females showed no change in TUNEL staining in any of the nuclei studied, but increased active caspase-3 in the hypoglossal, DMNV and NSTT ( P<0.05 for each). These results show for the first time that postnatal nicotine exposure can lead to an increase in apoptotic markers in the brain. In piglets, these effects showed regional and gender-specific differences, suggesting that passive, postnatal nicotine exposure may be responsible for some neuropathological changes observed in infants dying from SIDS.

Long-term nicotine exposure reduces Purkinje cell number in the adult rat cerebellar vermis

Nicotine affects functions of the central nervous system. A previous study showed that developing cerebellar Purkinje cells are targets for early postnatal nicotine exposure. In this study, we assessed the effects of long-term nicotine exposure on mature cerebellar Purkinje cells. This is particularly relevant since the majority of smokers are exposed to nicotine over a long period. Female adult Sprague–Dawley rats received three doses of nicotine (0.01%, 0.03%, or 0.06%) through their sole water source. After 8 weeks of nicotine exposure, the cerebellar vermis was removed and processed for stereological cell counting. The results showed that this long-term nicotine treatment did not change the cerebellum weight or the size (volume) of the cerebellar vermis. The long-term nicotine treatment regimen did result in a significant loss of mature Purkinje cells in the cerebellum, however, such a loss of Purkinje cells was not nicotine dose-related. These findings indicated that the mature adult cerebellum is susceptible to the damaging effects of nicotine in depleting Purkinje cells in the cerebellum.

Impaired cardiorespiratory recovery after laryngeal stimulation in nicotine-exposed young lambs.

The hypothesis that postnatal nicotine exposure weakens cardiorespiratory recovery from reflex apnea and bradycardia was tested in eight lambs continuously infused with nicotine from the day of birth at a dose of 1 to 2 mg.kg(-1).d(-1). Eight age-matched lambs infused with saline served as controls. Apnea and bradycardia were elicited by laryngeal stimulation with 1 mL of water (laryngeal chemoreflex) both during air breathing [0.21 fraction of inspired oxygen (FiO(2))] and mild hypoxia (0.10 FiO(2)) at a mean postnatal age of 5 +/- 1, 14 +/- 1, and 28 +/- 1 d. Ventilation, heart rate, and blood pressure were similar in the two groups at rest. In response to laryngeal chemoreflex stimulation, nicotine-treated lambs had a more pronounced decrease in ventilation (p < 0.05), longer reflex apnea (p < 0.001 in 0.21 FiO(2); p < 0.01 in 0.10 FiO(2)), and greater reflex bradycardia (p < 0.01). During reflex apnea, sighs were less efficient in restoring heart rate to prestimulation level, and a greater decrease in heart rate was observed before sighs in nicotine-treated lambs. These effects were most apparent at 5 d of age, when nicotine-treated lambs also had lower ventilation during hypoxia (p < 0.05). The response to hyperoxia was comparable in the two groups at all ages. The ability to terminate laryngeal chemoreflex-induced apnea is attenuated in young lambs continuously exposed to nicotine. This attenuation is present both in normoxia and in hypoxia and is accompanied by reduced effects from sighing on cardiac autoresuscitation.

Nicotinic receptor expression following nicotine exposure via maternal milk.

Studies have shown nicotine is excreted into maternal milk, so that suckling offspring would be a target of the drug during the pre-weaning period. Since nicotine exposure leads to an upregulation of neuronal nicotinic receptors, this study examines the hypothesis that nicotine delivered via maternal milk is capable of altering neuronal nicotinic receptor regulation in the drug-exposed rat pups. The present study showed that postnatal nicotine exposure via maternal milk was sufficient to induce an upregulation in brain nicotinic receptors similar to that seen in adults that smoke. Such exposure may result in altered neuronal development and synaptic activity and structure, potentially leading to long-term behavioral, learning, and memory deficits.

Prenatal nicotine affects catecholamine gene expression in newborn rat carotid body and petrosal ganglion.

Nicotine exposure modifies the expression of catecholamine and opioid neurotransmitter systems involved in attenuation of hypoxic chemosensitivity. We used in situ hybridization histochemistry to determine the effect of prenatal and early postnatal nicotine exposure on tyrosine hydroxylase (TH), dopamine beta-hydroxylase (DbetaH), preproenkephalin (PPE), and D2-dopamine receptor mRNA levels in the rat carotid body and petrosal ganglion during postnatal development. In the carotid body, nicotine increased TH mRNA expression in animals at 0 and 3 postnatal days (both, P < 0.05 vs. control) without affecting TH mRNA levels at 6 and 15 days. At 15 postnatal days, DbetaH mRNA levels were increased in the carotid body of nicotine-exposed animals. Dopamine D2-receptor mRNA levels in the carotid body increased with postnatal age but were unaffected by nicotine exposure. PPE was not expressed in the carotid body at any of the ages studied in control or treated animals. In the petrosal ganglion, nicotine increased the number of ganglion cells expressing TH mRNA in animals at 3 days (P < 0.01 vs. control). DbetaH mRNA expression was not induced nor was PPE mRNA expression increased in the petrosal ganglion in treated animals. Prenatal nicotine exposure upregulates mRNAs involved in the synthesis of two inhibitory neuromodulators, dopamine and norepinephrine, in peripheral arterial chemoreceptors, which may contribute to abnormalities in cardiorespiratory control observed in nicotine exposed animals.

Hepatotoxicity of prenatal and postnatal exposure to nicotine in rat pups.

Prenatal and postnatal exposure to nicotine have been shown to affect developing tissues in growing animals. Rat pups were exposed to nicotine prenatally and/or postnatally for 10 days by feeding pregnant and lactating rat dams water containing 0, 54, or 108 microM of nicotine. Nicotine exposure did not affect either litter sizes or body weights at birth and at 10 days of age. Exposure to 108 microM of nicotine prenatally increased significantly the incidence of focal necrosis at birth, and the liver damage was still evident at 10 days of age even after the pups were allowed to suckle dams not exposed to any nicotine during the study period. Continuation of nicotine exposure postnatally increased the incidence and severity of focal and confluent necrosis. Postnatal exposure to 108 microM of nicotine to pups not previously exposed also increased the incidence of mild focal and confluent necrosis, although not significantly. Exposure to nicotine prenatally did not affect liver malondialdehyde (MDA) levels at birth. However, liver MDA was significantly lower in rat pups exposed to nicotine prenatally when they were 10 days of age irrespective of whether there were further exposure to nicotine postnatally. Reasons for the late onset of the low MDA levels need further investigation. Postnatal nicotine exposure to either 54 or 108 microM of nicotine to pups not previously exposed fails to affect liver MDA at 10 days of age. The significant decrease in hepatic superoxide dismutase (SOD) levels reflects those of hepatic injury, indicating the possibility of a nicotine-induced downregulation of SOD enzyme production.

Sleep influences on homeostatic functions: implications for sudden infant death syndrome

The mechanisms underlying the sudden infant death syndrome (SIDS) appear to have origins in the fetal environment resulting in neural damage which later compromises responses to breathing or blood pressure challenges during sleep. The deficits appear to involve alterations in neurotransmitter receptors within regions involved in chemoreception and cardiovascular control. SIDS risk is enhanced by pre- and postnatal nicotine exposure, and possibly by hypoxic experiences. The prone sleeping position plays a significant role in risk, as do head positions that minimize facial escape from enclosed spaces; elevated body temperature may also be a factor. Compensatory mechanisms, including diminished gasping ability, relative failure to arouse to a safer state, or a failure to recruit respiratory efforts to overcome a blood pressure loss have been the object of recent research efforts. The findings suggest that the fatal event involves a neurally-compromised infant, circumstances that challenge vital physiology, most likely during sleep, at a particular developmental period.

Locomotor behavioral effects of prenatal and postnatal nicotine exposure in rat offspring.

The purpose of this study was to determine if prenatal/postnatal nicotine exposure results in hyperactive offspring. Rat offspring were exposed to nicotine, through implantation of osmotic minipumps in dams, at levels of 0.75, 1.5 and 3.0 mg/kg/day, for 19 days prenatally and 16 days postnatally. Offspring were measured for gestation length, body weight, litter size, sex difference and locomotor activity. No significant effects were shown for gestation length, litter size or male to female pup ratio. However, higher percentage of pup deaths resulted from nicotine-exposed dams than from control dams. Significantly less litter body weight was shown in nicotine-exposed offspring on postnatal day 1 when compared to controls. However, these offspring surpassed the control groups in litter body weight on postnatal day 14 and 21. Hyperactivity was shown in offspring exposed to prenatal/postnatal nicotine at levels of 0.75 and 3.0 mg/kg/day on postnatal day 14, but not on postnatal day 21 or at the 1.5 mg/kg/day condition. Results are consistent with the hypothesis that rat offspring are susceptible to the neurochemical and neurobehavioral effects of prenatal/postnatal nicotine exposure.

Postnatal Nicotine Exposure Does Not Further Enhance Breathing Pattern Alterations Suggestive of Impaired Lung Function in Prenatally Nicotine-Exposed Lambs

Postnatal Nicotine Exposure Does Not Further Enhance Breathing Pattern Alterations Suggestive of Impaired Lung Function in Prenatally Nicotine-Exposed Lambs

Cholinergic receptors in heart and brainstem of rats exposed to nicotine during development: implications for hypoxia tolerance and perinatal mortality

Cigarette smoking during pregnancy increases the incidence of perinatal mortality and Sudden Infant Death Syndrome (SIDS). We have evaluated prenatal or postnatal nicotine exposure in developing rats to examine the potential role of altered neurotransmitter receptor expression in these processes. Pregnant rats received continuous infusions of nicotine throughout gestation, at doses mimicking the plasma levels found in smokers. After birth, cardiac M2-muscarinic cholinergic receptors, which are responsible for inhibitory autonomic actions, were enhanced in the nicotine group, coincidentally with decreases in stimulatory β-adrenergic receptors that have been demonstrated previously. Studies of adenylyl cyclase activity confirmed that the changes in receptor binding represented functional alterations: the stimulatory response to isoproterenol was obtunded by prenatal nicotine exposure, whereas the inhibitory response to carbachol was enhanced. Elevations of M2-muscarinic receptor binding were not generalized to all tissues, as the same prenatal nicotine treatment elicited a reduction in these receptors in the brainstem, an effect that has also been noted in infants who died of SIDS; we found no effects of prenatal nicotine on brainstem M1-receptor binding. Postnatal administration of nicotine produced similar brainstem receptor effects when treatment was conducted during the first postnatal week but not thereafter; postnatal nicotine treatment did not affect cardiac M2-receptor binding. Thus, during a critical developmental period, nicotine exposure produces cardiac and brainstem receptor imbalances that favor inhibitory responses, effects that can contribute to morbidity and mortality evoked by hypoxic episodes, such as those experienced during parturition, sleep apnea or airway obstruction.

Effect of pre- and postnatal nicotine exposure on vasopressinergic system in rats

Timed pregnant Sprague–Dawley rats were infused subcutaneously either with nicotine (NIC, 6 mg kg −1 day −1; n=17) or saline (control, n=15) on the 3rd day of gestation, via Alzet osmotic pumps, for 28 days. After the parturition, the pups of both, control and NIC infused dams, were each randomly divided into 2 groups and placed to be nursed as following: (1) control dams nursing pups born to control mother (control group); (2) control dams nursing pups born to NIC-infused mother (prenatal NIC group); (3) NIC-infused dams nursing pups born to control mother (postnatal NIC group); (4) NIC-infused dams nursing pups born to NIC-infused mother (pre- and postnatal NIC group). Vasopressin (VP) was measured by RIA in plasma, neurointermediate lobe (NIL) and hypothalamus (HT) in the pups of both sexes, at the following age: 0 (within 24 h after birth); 1, 2, 3, 4 and 6 weeks. At the age of 3, 4 and 6 weeks, the isolated NILs were individually superfused and VP was measured as a basal release and the response to a 10-min 56 mM potassium stimulation. A marked suppression in the activity of VP-ergic system was observed in both sexes of offspring exposed to NIC prenatally, being first detectable at the age of 3 weeks, when the HT-NIL system becomes fully developed. However, the significant changes were observed at the age of 6 weeks: decreased serum VP concentration, lower VP contents in the HT and NIL, and suppressed VP release, basal and stimulated, from the isolated NIL. Postnatal exposure to nicotine was ineffective.