Repeated ketamine anesthesia during neurodevelopment upregulates hippocampal activity and enhances drug reward in male mice View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2022-07-15

AUTHORS

Jianchen Cui, Xianshu Ju, Yulim Lee, Boohwi Hong, Hyojin Kang, Kihoon Han, Won-Ho Shin, Jiho Park, Min Joung Lee, Yoon Hee Kim, Youngkwon Ko, Jun Young Heo, Woosuk Chung

ABSTRACT

Early exposures to anesthetics can cause long-lasting changes in excitatory/inhibitory synaptic transmission (E/I imbalance), an important mechanism for neurodevelopmental disorders. Since E/I imbalance is also involved with addiction, we further investigated possible changes in addiction-related behaviors after multiple ketamine anesthesia in late postnatal mice. Postnatal day (PND) 16 mice received multiple ketamine anesthesia (35 mg kg−1, 5 days), and behavioral changes were evaluated at PND28 and PND56. Although mice exposed to early anesthesia displayed normal behavioral sensitization, we found significant increases in conditioned place preference to both low-dose ketamine (20 mg kg−1) and nicotine (0.5 mg kg−1). By performing transcriptome analysis and whole-cell recordings in the hippocampus, a brain region involved with CPP, we also discovered enhanced neuronal excitability and E/I imbalance in CA1 pyramidal neurons. Interestingly, these changes were not found in female mice. Our results suggest that repeated ketamine anesthesia during neurodevelopment may influence drug reward behavior later in life. More... »

PAGES

709

Identifiers

URI

http://scigraph.springernature.com/pub.10.1038/s42003-022-03667-4

DOI

http://dx.doi.org/10.1038/s42003-022-03667-4

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1149496285

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/35840630


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26 schema:description Early exposures to anesthetics can cause long-lasting changes in excitatory/inhibitory synaptic transmission (E/I imbalance), an important mechanism for neurodevelopmental disorders. Since E/I imbalance is also involved with addiction, we further investigated possible changes in addiction-related behaviors after multiple ketamine anesthesia in late postnatal mice. Postnatal day (PND) 16 mice received multiple ketamine anesthesia (35 mg kg−1, 5 days), and behavioral changes were evaluated at PND28 and PND56. Although mice exposed to early anesthesia displayed normal behavioral sensitization, we found significant increases in conditioned place preference to both low-dose ketamine (20 mg kg−1) and nicotine (0.5 mg kg−1). By performing transcriptome analysis and whole-cell recordings in the hippocampus, a brain region involved with CPP, we also discovered enhanced neuronal excitability and E/I imbalance in CA1 pyramidal neurons. Interestingly, these changes were not found in female mice. Our results suggest that repeated ketamine anesthesia during neurodevelopment may influence drug reward behavior later in life.
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32 schema:keywords CA1 pyramidal neurons
33 CPP
34 PND28
35 PND56
36 activity
37 addiction
38 addiction-related behaviors
39 analysis
40 anesthesia
41 anesthetics
42 behavior
43 behavioral changes
44 behavioral sensitization
45 brain regions
46 changes
47 disorders
48 drug reward
49 drug reward behaviors
50 early anesthesia
51 early exposure
52 excitability
53 excitatory/inhibitory synaptic transmission
54 exposure
55 female mice
56 hippocampal activity
57 hippocampus
58 important mechanism
59 increase
60 inhibitory synaptic transmission
61 ketamine
62 ketamine anesthesia
63 late postnatal mice
64 life
65 low-dose ketamine
66 male mice
67 mechanism
68 mice
69 neurodevelopment
70 neurodevelopmental disorders
71 neuronal excitability
72 neurons
73 nicotine
74 place preference
75 possible changes
76 postnatal mice
77 preferences
78 pyramidal neurons
79 recordings
80 region
81 results
82 reward
83 reward behavior
84 sensitization
85 significant increase
86 synaptic transmission
87 transcriptome analysis
88 transmission
89 whole-cell recordings
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