Nicotine Exposure during the Third Trimester Equivalent of Human Gestation: Time Course of Effects on the Central Cholinergic System of Rats

Nunes‐Freitas, André L.; Ribeiro‐Carvalho, Anderson; Lima, Carla S.; Dutra-Tavares, Ana Carolina; Manhães, Alex C.; Lisboa, Patrícia Cristina; Oliveira, Elaine de; Moura, Egberto Gaspar de; Filgueiras, Cláudio C.; Abreu‐Villaça, Yael

doi:10.1093/toxsci/kfr147

Cited by 23 publications

(16 citation statements)

References 65 publications

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“…There is a biological basis for the associations between third trimester PCSE and offspring nicotine dependence. Laboratory research has found that in the third trimester of gestation, brain development is highly susceptible to nicotine (Nunes-Freitas et al, 2011; Slotkin, 2008; Lotfipour et al, 2010), and exposure during this time might be more likely to predict greater levels of problematic tobacco use. In a study by Slotkin (2008), there was an upregulation of nicotinic acetylcholine receptors (nAChR) among adult rats exposed to nicotine in the immediate neonatal period, a time comparable to the third trimester in humans.…”

Section: Discussionmentioning

confidence: 99%

Prenatal cigarette smoking: Long-term effects on young adult behavior problems and smoking behavior

Cornelius

Goldschmidt

Day

2012

Neurotoxicology and Teratology

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We examined the long-term effects of prenatal cigarette smoke exposure (PCSE) on the behavior problems and smoking behavior of 22-year-old offspring. The mothers of these offspring were interviewed about their tobacco and other drug use during pregnancy at the fourth and seventh gestational months, and at delivery. Data on the offspring are from interviews at age 22 (n=608). Behavior problems were measured by the Adult Self-Report (ASR) with the following outcome scales: total behavior problems, externalizing, internalizing, attention, anxiety/depression, withdrawn, thought, intrusive, aggression, somatic and rule breaking behavioral problems. Young adult smoking behavior was measured using self-reported average daily cigarettes, and was validated with urine cotinine. Nicotine dependence was measured with the Fagerström Tobacco and Nicotine Dependence (FTND) scale. Regression analyses tested the relations between trimester-specific PCSE and young adult’s behavioral problems and smoking behavior, adjusting for demographic and maternal psychological characteristics, and other prenatal substance exposures. Exposed young adults had significantly higher scores on the externalizing, internalizing, aggression, and somatic scales of the ASR. These young adults were also more likely to have a history of arrests. Young adults with PCSE also had a higher rate of smoking and nicotine dependence. Our previous findings of the relations between PCSE and aggressive behavior in early childhood and PCSE and smoking behavior in early adolescence extend into young adulthood.

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Section: Discussionmentioning

confidence: 99%

Prenatal cigarette smoking: Long-term effects on young adult behavior problems and smoking behavior

Cornelius

Goldschmidt

Day

2012

Neurotoxicology and Teratology

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“…We evaluated nAChRs binding in left cerebral cortex, midbrain and hippocampus. The nAChRs binding method has been described in detail in previous papers (Abreu-Villaca et al, 2016;Lima et al, 2013;Nunes-Freitas et al, 2011;Ribeiro-Carvalho et al, 2008;Ribeiro-Carvalho et al, 2009). Briefly, tissues were thawed and homogenized (Ultra-Turrax T10 basic, IKA, São Paulo, SP) in 40 vols of ice-cold 50 mM Tris-HCl (pH 7.4), the homogenates were sedimented at 40,000 × g for 10 min and the supernatant solution was discarded.…”

Section: Nachrs Bindingmentioning

confidence: 99%

“…Aliquots were withdrawn for measurements of [3H]cytisine binding and for membrane protein evaluation (Bicinchoninic Acid kit). [3H]cytisine is a selective ligand that binds to the α4β2 nAChR, the predominant receptor subtype in the mammalian brain, and that is upregulated by nicotine (Abreu-Villaca et al, 2003;Nunes-Freitas et al, 2011;Ribeiro-Carvalho et al, 2008). Binding was determined using a final ligand concentration of 2 nM; specific binding was displaced with 100 μM nicotine.…”

Section: Nachrs Bindingmentioning

confidence: 99%

Maternal undernutrition during lactation alters nicotine reward and DOPAC/dopamine ratio in cerebral cortex in adolescent mice, but does not affect nicotine‐induced nAChRs upregulation

Dutra-Tavares

Silva

Nunes‐Freitas

et al. 2017

Intl J of Devlp Neuroscience

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Early undernutrition causes long lasting alterations that affect the response to psychoactive drugs. Particularly, undernutrition during lactation affects the acute locomotor response to nicotine during adolescence, but the reward effect of continued exposure to nicotine remains unknown. The goal of this study was to investigate the effects of undernutrition during lactation on the nicotine susceptibility indexed via conditioned place preference (CPP), on dopamine content and turnover and on nicotine-induced nicotinic cholinergic receptor (nAChR) upregulation in the cerebral cortex, midbrain and hippocampus of adolescent mice. The impact of undernutrition and nicotine exposure on stress-related hormones and leptin was also investigated. From postnatal day 2 (PN2) to weaning (PN21), dams were randomly assigned to one of the following groups: Control (C) - free access to standard laboratory diet (23% protein); Protein Restricted (PR) - free access to isoenergenetic diet (8% protein); Calorie Restricted (CR) - access to standard laboratory diet in restricted quantities (mean ingestion of PR). PR and CR groups showed less mass gain and less visceral fat mass. While C and CR were equally susceptible to nicotine-induced place preference conditioning, PR failed to show a conditioning pattern. In contrast, all groups presented a nicotine-evoked nAChR upregulation in the cerebral cortex. While dopamine and DOPAC levels did not differ between groups, the DOPAC/dopamine ratio was increased in CR animals. No differences in endocrine parameters were observed. Taken together, our results indicate that undernutrition during lactation programs for brain alterations later in life. Our data also suggest that early undernutrition does not affect the rewarding associative properties of nicotine at adolescence.

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“…All assays have been described in detail in previous papers (Lima et al, 2013;Nunes-Freitas et al, 2011;Ribeiro-Carvalho et al, 2008) and will therefore be presented briefly. ChAT activity was assayed in tissue homogenate using 50 M [ 14 C]Acetylcoenzyme A.…”

Section: Aliquots Of This Resuspension Were Withdrawn For Measurementmentioning

confidence: 99%

A ten fold reduction of nicotine yield in tobacco smoke does not spare the central cholinergic system in adolescent mice

Abreu‐Villaça

Correa-Santos

Dutra-Tavares

et al. 2016

Intl J of Devlp Neuroscience

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The tobacco industry has gradually decreased nicotine content in cigarette smoke but the impact of this reduction on health is still controversial. Since the central cholinergic system is the primary site of action of nicotine, here, we investigated the effects of exposure of adolescent mice to tobacco smoke containing either high or low levels of nicotine on the central cholinergic system and the effects associated with cessation of exposure. From postnatal day (PN) 30 to 45, male and female Swiss mice were exposed to tobacco smoke (whole body exposure, 8h/day, 7 days/week) generated from 2R1F (HighNic group: 1.74mg nicotine/cigarette) or 4A1 (LowNic group: 0.14mg nicotine/cigarette) research cigarettes, whereas control mice were exposed to ambient air. Cholinergic biomarkers were assessed in the cerebral cortex and midbrain by the end of exposure (PN45), at short- (PN50) and long-term (PN75) deprivation. In the cortex, nicotinic cholinergic receptor upregulation was observed with either type of cigarette. In the midbrain, upregulation was detected only in HighNic mice and remained significant in females at short-term deprivation. The high-affinity choline transporter was reduced in the cortex: of HighNic mice by the end of exposure; of both HighNic and LowNic females at short-term deprivation; of LowNic mice at long-term deprivation. These decrements were separable from effects on choline acetyltransferase and acetylcholinesterase activities, suggesting cholinergic synaptic impairment. Here, we demonstrated central cholinergic alterations in an animal model of tobacco smoke exposure during adolescence. This system was sensitive even to tobacco smoke with very low nicotine content.

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Nicotine Exposure during the Third Trimester Equivalent of Human Gestation: Time Course of Effects on the Central Cholinergic System of Rats

Cited by 23 publications

References 65 publications

Prenatal cigarette smoking: Long-term effects on young adult behavior problems and smoking behavior

Prenatal cigarette smoking: Long-term effects on young adult behavior problems and smoking behavior

Maternal undernutrition during lactation alters nicotine reward and DOPAC/dopamine ratio in cerebral cortex in adolescent mice, but does not affect nicotine‐induced nAChRs upregulation

A ten fold reduction of nicotine yield in tobacco smoke does not spare the central cholinergic system in adolescent mice

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