Cited by 59Anesthesia and Neurotoxicity ResearchPrenatal Substance Exposure EffectsNeuroscience and Neuropharmacology Research

Prenatal ketamine exposure causes abnormal development of prefrontal cortex in rat

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Zhao, Tianyun, Li, Chuanxiang, Wei, Wei, Zhang, Haixing, Ma, Daqing, Song, Xingrong, Zhou, Libing·2016·Scientific Reports

Abstract

Ketamine is commonly used for anesthesia and as a recreational drug. In pregnant users, a potential neurotoxicity in offspring has been noted. Our previous work demonstrated that ketamine exposure of pregnant rats induces affective disorders and cognitive impairments in offspring. As the prefrontal cortex (PFC) is critically involved in emotional and cognitive processes, here we studied whether maternal ketamine exposure influences the development of the PFC in offspring. Pregnant rats on gestational day 14 were treated with ketamine at a sedative dose for 2 hrs, and pups were studied at postnatal day 0 (P0) or P30. We found that maternal ketamine exposure resulted in cell apoptosis and neuronal loss in fetal brain. Upon ketamine exposure in utero, PFC neurons at P30 showed more dendritic branching, while cultured neurons from P0 PFC extended shorter neurites than controls. In addition, maternal ketamine exposure postponed the switch of NR2B/2A expression, and perturbed pre- and postsynaptic protein expression in the PFC. These data suggest that prenatal ketamine exposure impairs neuronal development of the PFC, which may be associated with abnormal behavior in offsprings.

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  • Similar structural and behavioral defects of the PFC can be observed in kids with prenatal exposure to opioids, cocaine, amphetamines and other drugs-of-abuse.

    “Similar structural and behavioral defects of the PFC can be observed in kids with prenatal exposure to opioids, cocaine, amphetamines and other drugs-of-abuse [322–330].”

    From Development of prefrontal cortex (2022) · cites this paper as [330]

    The Results and Discussion report PFC structural abnormalities in rat offspring after prenatal ketamine exposure and relate them to behavioral impairments. The Discussion also mentions reports of increased PFC spine density after exposure to amphetamine, cocaine, or nicotine. This copy does not establish similar structural and behavioral PFC defects in children prenatally exposed to opioids, cocaine, or amphetamines. (LLM, conf=0.87)

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Research works printed but not linked: 2

  1. Godsil B. P., Kiss J. P., Spedding M. & Jay T. M. The hippocampal-prefrontal pathway: the weak link in psychiatric disorders? Eur Neuropsychopharmacol 23, 1165– 1181 (2013). 23332457
  2. Jevtovic-Todorovic V. et al. Anaesthetic neurotoxicity and neuroplasticity: an expert group report and statement based on the BJA Salzburg Seminar. Br J Anaesth 111, 143– 151 (2013). 23722106 PMC3711392

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Authors
Zhao, T., Li, C., Wei, W., Zhang, H., Ma, D., Song, X., & Zhou, L.
Affiliations
  • Guangzhou Women and Children Medical Center (CN)
  • Third Affiliated Hospital of Southern Medical University (CN)
  • Chelsea and Westminster Hospital (GB)
  • Jinan University (CN)
Corresponding author
  • Song, Xingrong
  • Zhou, Libing
Venue
Scientific Reports
Published
2016-05-26
Volume
6
Issue
1
Pages
26865-26865
ISSN
2045-2322 (ISSN-L)
OpenAlex
W2398744811
Cited by
59
References
48
Citations by year
2026: 2 · 2025: 6 · 2024: 3 · 2023: 9 · 2022: 6 · 2021: 5 · 2020: 7 · 2019: 6 · 2018: 8 · 2017: 4 · 2016: 3
FWCI
3.57
Type
journal article
Language
en
Open access
Locations
  • Scientific Reports (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • Spiral (Imperial College London) (submittedVersion, cc-by)
Funders
  • National Natural Science Foundation of China (973 Program, 2014CB542205, B14036)
  • National Key Research and Development Program of China (2014CB542205)
Topics
  • Life Sciences › Neuroscience › Developmental Neuroscience › Anesthesia and Neurotoxicity Research
  • Health Sciences › Medicine › Pediatrics, Perinatology and Child Health › Prenatal Substance Exposure Effects
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
Keywords
prefrontal cortex development, prenatal drug exposure, developmental neurotoxicity, apoptosis, neuronal loss, dendritic branching, neurite length, synaptic proteins, offspring behavior
MeSH terms
Abnormalities, Drug-Induced, Disks Large Homolog 4 Protein, Anesthetics, Dissociative, Animals, Brain, Cells, Cultured, Female, Gestational Age, Hypnotics and Sedatives, Ketamine, Neurons, Pregnancy, Prenatal Exposure Delayed Effects, Random Allocation, Illicit Drugs, Receptors, N-Methyl-D-Aspartate, Neurites, Synaptophysin, Rats, Sprague-Dawley, Apoptosis, Prefrontal Cortex, Excitatory Amino Acid Antagonists, Rats

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