Prenatal nicotine effects on memory in rats: pharmacological and behavioral challenges
Abstract
Cigarette smoking during pregnancy has been shown in a variety of studies to be associated with cognitive deficits in the children. Nicotine administration to rats during gestation has been found to cause subtle cognitive effects in the offspring. Some individual differences in cognitive impairment may be related to prenatal nicotine effects on noradrenergic (NE) systems. In the current study, 10 Sprague-Dawley rat dams were infused with approximately 2 mg/kg/day of nicotine ditartrate via osmotic minipumps and 10 control dams were exposed to vehicle-containing minipumps from gestational day (GD) 4-20. Starting on postnatal day (PND) 50, the offspring were tested for T-maze rewarded spatial alternation with intertrial intervals of 0, 10, 20, or 40 s. There was a sex- and delay-dependent effect of prenatal nicotine exposure on T-maze alternation. Nicotine-exposed males showed a significant deficit at the 0 s delay. In radial-arm maze (RAM) acquisition training there were no significant nicotine effects. However, significant nicotine-related effects were seen with subsequent behavioral and pharmacological challenges in the RAM. Changing the RAM testing location to an identical maze in a different room elicited a significant choice accuracy deficit in the prenatal nicotine-exposed rats compared with controls. Acute nicotine challenge did not cause any differential effects in the prenatal nicotine and control groups. During the isoproterenol (beta-NE agonist) challenge phase there appeared a significant facilitation of choice accuracy and speeding of response in the prenatal nicotine exposure group which was not seen in the control group. The alpha-NE agonist phenylpropanolamine caused a significant deficit in control females but not in the females prenatally exposed to nicotine. No differential effects of the alpha-NE antagonist phenoxybenzamine were seen in the prenatal nicotine and control groups. Throughout RAM testing there was a significant sex effect with males having better choice accuracy than females. These results demonstrate that the persisting cognitive effects of prenatal exposure to 2 mg/kg/day cause subtle effects in cognitive performance which can be elicited with behavioral and pharmacological challenge. These results also support previous studies suggesting the involvement of NE systems in persisting effects of prenatal nicotine exposure.
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Animal studies of prenatal nicotine exposure and cognitive development are more consistent, suggesting global learning and memory impairments.
“there is greater consistency among animal studies examining the effects of prenatal nicotine exposure on cognitive development, suggestive of global impairments in learning and memory.”
From Developmental toxicity of nicotine: A transdisciplinary synthesis and implications for emerging tobacco products (2017) · cites this paper as [185]
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- Authors
- Levin, E. D., Wilkerson, A., Jones, J. P., Channelle Christopher, N., & Briggs, S. J.
- Affiliations
- Duke University (US)
- Duke Medical Center (US)
- Corresponding author
- Levin, Edward D.
- Venue
- Developmental Brain Research
- Publisher
- Elsevier BV
- Published
- 1996-12
- Volume
- 97
- Issue
- 2
- Pages
- 207-215
- ISSN
- 0165-3806 (ISSN-L)
- OpenAlex
- W2037441262
- Cited by
- 137
- References
- 3
- Citations by year
- 2026: 1 · 2025: 1 · 2023: 2 · 2022: 6 · 2021: 5 · 2020: 3 · 2019: 4 · 2018: 4 · 2017: 4 · 2016: 3 · 2015: 6 · 2014: 4 · 2013: 5 · 2012: 8
- FWCI
- 5.08
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Developmental Brain Research (publishedVersion)
- PubMed (publishedVersion)
- Funders
- March of Dimes Foundation
- Topics
- Health Sciences › Medicine › Pediatrics, Perinatology and Child Health › Prenatal Substance Exposure Effects
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Nicotinic Acetylcholine Receptors Study
- Health Sciences › Medicine › Physiology › Smoking Behavior and Cessation
- Keywords
- prenatal nicotine exposure, maternal smoking, cognitive impairment, spatial memory, noradrenergic system, sex differences, delayed alternation, radial maze, isoproterenol challenge, phenoxybenzamine
- MeSH terms
- Animals, Drug Evaluation, Preclinical, Female, Infusion Pumps, Male, Memory Disorders, Nicotine, Osmotic Pressure, Pregnancy, Prenatal Exposure Delayed Effects, Receptors, Adrenergic, Rats, Sprague-Dawley, Sex Distribution, Nicotinic Agonists, Maze Learning, Rats
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