Prenatal nicotine exposure changes natural and drug‐induced reinforcement in adolescent male rats
Abstract
Clinical studies have demonstrated an increased incidence of substance misuse and obesity in adolescents whose mothers smoked during pregnancy. Although dopamine systems that mediate natural and drug‐induced reinforcement have been shown in animal studies to be altered by gestational nicotine treatment, it is not clear whether there are concomitant changes in reinforcement sensitivity. To test whether prenatal nicotine exposure influences sensitivity to natural and drug rewards, timed pregnant rats were implanted with osmotic minipumps delivering saline or nicotine (3 mg/kg/day) from gestational day 4 to 18. Male offspring were tested as adolescents, on postnatal day 32, for operant responding maintained by sucrose pellets or i.v. cocaine (200 or 500 μg/kg per injection). Cocaine‐induced stereotypy and c‐fos mRNA expression in cortex and striatum were also examined. Complex changes in reward circuitry were observed in the offspring of nicotine‐exposed dams. Nicotine‐exposed adolescents did not self‐administer the low dose of cocaine, but, at the higher dose, exhibited significantly greater cocaine intake and c‐fos mRNA expression in nucleus accumbens than did controls. In contrast, control animals showed significantly greater drug‐induced stereotypy at both cocaine doses. Operant responding maintained by sucrose was also influenced by gestational nicotine exposure. At a fixed ratio (FR) 1 schedule, although the number of pellets eaten by the two experimental groups was equivalent, more pellets were left uneaten by nicotine‐exposed offspring. At FR2 and FR5 schedules, the responding maintained by sucrose pellets was lower in nicotine‐exposed offspring. These findings suggest that nicotine exposure during gestation may induce changes in both natural and drug reward pathways.
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Prenatal maternal smoking is associated with long-term adverse effects extending into childhood and adolescence, including increased risk for ADHD, obesity, schizophrenia, and adolescent substance abuse and dependence.
“Prenatal maternal smoking has also been associated with long-term adverse effects that extend into childhood and adolescence such as an increased risk for ADHD, obesity, schizophrenia, and adolescent substance abuse and dependence (Figure 1)”
From Prenatal nicotine exposure during pregnancy results in adverse neurodevelopmental alterations and neurobehavioral deficits (2023) · cites this paper as [11]
Clinical and animal studies have demonstrated an increased incidence of obesity in adolescents whose mothers smoked during pregnancy.
“Clinical and animal studies have demonstrated an increased incidence of obesity in adolescents whose mothers smoked during pregnancy [11, 143, 144].”
From Prenatal nicotine exposure during pregnancy results in adverse neurodevelopmental alterations and neurobehavioral deficits (2023) · cites this paper as [11]
Clinical and animal studies have demonstrated an increased incidence of adolescent substance abuse in adolescents whose mothers smoked during pregnancy.
“Clinical and animal studies have demonstrated an increased incidence of adolescent substance abuse in adolescents whose mothers smoked during pregnancy [11, 143, 144].”
From Prenatal nicotine exposure during pregnancy results in adverse neurodevelopmental alterations and neurobehavioral deficits (2023) · cites this paper as [11]
The increased obesity later in life likely reflects a greater preference for high caloric and palatable foods that activate the reward pathways.
“which likely reflects a greater preference for high caloric and palatable foods that activate the reward pathways [11]”
From Prenatal nicotine exposure during pregnancy results in adverse neurodevelopmental alterations and neurobehavioral deficits (2023) · cites this paper as [11]
Infants exposed to PN initially have low birth weights, but a subsequent increase in obesity is observed later in life.
“Although infants exposed to PN initially have low birth weights, a subsequent increase in obesity is observed later in life”
From Prenatal nicotine exposure during pregnancy results in adverse neurodevelopmental alterations and neurobehavioral deficits (2023) · cites this paper as [11]
Control rats showed significantly greater drug-induced stereotypy at both cocaine doses compared to PNE rats.
“In contrast to the PNE rats, the control rats showed significantly greater drug-induced stereotypy at both cocaine doses.”
From Prenatal nicotine exposure during pregnancy results in adverse neurodevelopmental alterations and neurobehavioral deficits (2023) · cites this paper as [11]
PNE induced complex changes in the offspring's reward circuitry with adolescent offspring not administering cocaine at low doses but exhibiting significantly greater cocaine intake and c-fos mRNA expression in the NA at higher doses than controls.
“They found that PNE induced complex changes in the offspring’s reward circuitry with the adolescent offspring not administering cocaine at low doses but exhibiting significantly greater cocaine intake and c-fos mRNA expression in the NA at higher doses than in the control group [11].”
From Prenatal nicotine exposure during pregnancy results in adverse neurodevelopmental alterations and neurobehavioral deficits (2023) · cites this paper as [11]
Adverse affective outcomes have been identified, including learned helplessness, fear trace conditioning, and anhedonia.
“Adverse outcomes on affective behavior have also been identified, including learned helplessness, fear trace conditioning, and anhedonia.”
From Developmental toxicity of nicotine: A transdisciplinary synthesis and implications for emerging tobacco products (2017) · cites this paper as [192]
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- Authors
- Franke, R. M., Park, M., Belluzzi, J. D., & Leslie, F. M.
- Affiliations
- St. Jude Children's Research Hospital (US)
- University of California, Irvine (US)
- Venue
- European Journal of Neuroscience
- Publisher
- Wiley
- Published
- 2008-06
- Volume
- 27
- Issue
- 11
- Pages
- 2952-2961
- ISSN
- 0953-816X (ISSN-L)
- 1460-9568
- OpenAlex
- W1978081138
- Cited by
- 71
- References
- 6
- Citations by year
- 2026: 1 · 2024: 1 · 2023: 2 · 2022: 5 · 2021: 2 · 2020: 5 · 2019: 2 · 2018: 3 · 2017: 4 · 2016: 5 · 2015: 6 · 2014: 6 · 2013: 6 · 2012: 5
- FWCI
- 5.41
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- European Journal of Neuroscience (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute on Drug Abuse (DA-10612, R01DA010612, DA 19318)
- Topics
- Health Sciences › Medicine › Pediatrics, Perinatology and Child Health › Prenatal Substance Exposure Effects
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Nicotinic Acetylcholine Receptors Study
- Keywords
- prenatal nicotine exposure, adolescent rats, cocaine self-administration, sucrose reward, natural reward, Fos expression, nucleus accumbens, dopaminergic system, reward sensitivity, maternal smoking, adolescent substance use
- MeSH terms
- Aging, Animals, Brain, Brain Chemistry, Cocaine, Conditioning, Operant, Dose-Response Relationship, Drug, Female, Male, Nicotine, Pregnancy, Prenatal Exposure Delayed Effects, Reinforcement, Psychology, RNA, Messenger, Self Administration, Smoking, Stereotyped Behavior, Tobacco Use Disorder, Causality, Proto-Oncogene Proteins c-fos, Rats, Sprague-Dawley, Nicotinic Agonists, Dopamine Uptake Inhibitors, Rats
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