Influence of nicotine on doxorubicin and cyclophosphamide combination treatment-induced spatial cognitive impairment and anxiety-like behavior in rats

Yoshihisa Kitamura, Erika Kanemoto, Misaki Sugimoto, Ayumi Machida, Yuka Nakamura, Nanami Naito, Hirotaka Kanzaki, Ikuko Miyazaki, Masato Asanuma, Toshiaki Sendo

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

In the present study, we examined the effects of nicotine on cognitive impairment, anxiety-like behavior, and hippocampal cell proliferation in rats treated with a combination of doxorubicin and cyclophosphamide. Combined treatment with doxorubicin and cyclophosphamide produced cognitive impairment and anxiety-like behavior in rats. Nicotine treatment reversed the inhibition of novel location recognition induced by the combination treatment. This effect of nicotine was blocked by methyllycaconitine, a selective α7 nicotinic acetylcholine receptor (nAChR) antagonist, and dihydro-β-erythroidine, a selective α4β2 nAChR antagonist. In addition, nicotine normalized the amount of spontaneous alternation seen during the Y-maze task, which had been reduced by the combination treatment. This effect of nicotine was inhibited by dihydro-β-erythroidine. In comparison, nicotine did not affect the anxiety-like behavior induced by the combination treatment. Furthermore, the combination treatment reduced the number of proliferating cells in the subgranular zone of the hippocampal dentate gyrus, and this was also prevented by nicotine. Finally, the combination of doxorubicin and cyclophosphamide significantly reduced hippocampal α7 nAChR mRNA expression. These results suggest that nicotine inhibits doxorubicin and cyclophosphamide-induced cognitive impairment via α7 nAChR and α4β2 nAChR, and also enhances hippocampal neurogenesis.

Original languageEnglish
Pages (from-to)369-378
Number of pages10
JournalNaunyn-Schmiedeberg's Archives of Pharmacology
Volume390
Issue number4
DOIs
Publication statusPublished - Apr 1 2017

Fingerprint

Nicotine
Doxorubicin
Cyclophosphamide
Anxiety
Nicotinic Receptors
Cholinergic Antagonists
Parahippocampal Gyrus
Cognitive Dysfunction
Neurogenesis
Dentate Gyrus
Cell Count
Cell Proliferation
Messenger RNA

Keywords

  • Anxiety
  • Cognitive impairment
  • Cyclophosphamide
  • Doxorubicin
  • Neurogenesis
  • Nicotine

ASJC Scopus subject areas

  • Pharmacology

Cite this

Influence of nicotine on doxorubicin and cyclophosphamide combination treatment-induced spatial cognitive impairment and anxiety-like behavior in rats. / Kitamura, Yoshihisa; Kanemoto, Erika; Sugimoto, Misaki; Machida, Ayumi; Nakamura, Yuka; Naito, Nanami; Kanzaki, Hirotaka; Miyazaki, Ikuko; Asanuma, Masato; Sendo, Toshiaki.

In: Naunyn-Schmiedeberg's Archives of Pharmacology, Vol. 390, No. 4, 01.04.2017, p. 369-378.

Research output: Contribution to journalArticle

@article{0bc81cca43704cdc818547e6dc18b245,
title = "Influence of nicotine on doxorubicin and cyclophosphamide combination treatment-induced spatial cognitive impairment and anxiety-like behavior in rats",
abstract = "In the present study, we examined the effects of nicotine on cognitive impairment, anxiety-like behavior, and hippocampal cell proliferation in rats treated with a combination of doxorubicin and cyclophosphamide. Combined treatment with doxorubicin and cyclophosphamide produced cognitive impairment and anxiety-like behavior in rats. Nicotine treatment reversed the inhibition of novel location recognition induced by the combination treatment. This effect of nicotine was blocked by methyllycaconitine, a selective α7 nicotinic acetylcholine receptor (nAChR) antagonist, and dihydro-β-erythroidine, a selective α4β2 nAChR antagonist. In addition, nicotine normalized the amount of spontaneous alternation seen during the Y-maze task, which had been reduced by the combination treatment. This effect of nicotine was inhibited by dihydro-β-erythroidine. In comparison, nicotine did not affect the anxiety-like behavior induced by the combination treatment. Furthermore, the combination treatment reduced the number of proliferating cells in the subgranular zone of the hippocampal dentate gyrus, and this was also prevented by nicotine. Finally, the combination of doxorubicin and cyclophosphamide significantly reduced hippocampal α7 nAChR mRNA expression. These results suggest that nicotine inhibits doxorubicin and cyclophosphamide-induced cognitive impairment via α7 nAChR and α4β2 nAChR, and also enhances hippocampal neurogenesis.",
keywords = "Anxiety, Cognitive impairment, Cyclophosphamide, Doxorubicin, Neurogenesis, Nicotine",
author = "Yoshihisa Kitamura and Erika Kanemoto and Misaki Sugimoto and Ayumi Machida and Yuka Nakamura and Nanami Naito and Hirotaka Kanzaki and Ikuko Miyazaki and Masato Asanuma and Toshiaki Sendo",
year = "2017",
month = "4",
day = "1",
doi = "10.1007/s00210-016-1338-z",
language = "English",
volume = "390",
pages = "369--378",
journal = "Naunyn-Schmiedeberg's Archives of Pharmacology",
issn = "0028-1298",
publisher = "Springer Verlag",
number = "4",

}

TY - JOUR

T1 - Influence of nicotine on doxorubicin and cyclophosphamide combination treatment-induced spatial cognitive impairment and anxiety-like behavior in rats

AU - Kitamura, Yoshihisa

AU - Kanemoto, Erika

AU - Sugimoto, Misaki

AU - Machida, Ayumi

AU - Nakamura, Yuka

AU - Naito, Nanami

AU - Kanzaki, Hirotaka

AU - Miyazaki, Ikuko

AU - Asanuma, Masato

AU - Sendo, Toshiaki

PY - 2017/4/1

Y1 - 2017/4/1

N2 - In the present study, we examined the effects of nicotine on cognitive impairment, anxiety-like behavior, and hippocampal cell proliferation in rats treated with a combination of doxorubicin and cyclophosphamide. Combined treatment with doxorubicin and cyclophosphamide produced cognitive impairment and anxiety-like behavior in rats. Nicotine treatment reversed the inhibition of novel location recognition induced by the combination treatment. This effect of nicotine was blocked by methyllycaconitine, a selective α7 nicotinic acetylcholine receptor (nAChR) antagonist, and dihydro-β-erythroidine, a selective α4β2 nAChR antagonist. In addition, nicotine normalized the amount of spontaneous alternation seen during the Y-maze task, which had been reduced by the combination treatment. This effect of nicotine was inhibited by dihydro-β-erythroidine. In comparison, nicotine did not affect the anxiety-like behavior induced by the combination treatment. Furthermore, the combination treatment reduced the number of proliferating cells in the subgranular zone of the hippocampal dentate gyrus, and this was also prevented by nicotine. Finally, the combination of doxorubicin and cyclophosphamide significantly reduced hippocampal α7 nAChR mRNA expression. These results suggest that nicotine inhibits doxorubicin and cyclophosphamide-induced cognitive impairment via α7 nAChR and α4β2 nAChR, and also enhances hippocampal neurogenesis.

AB - In the present study, we examined the effects of nicotine on cognitive impairment, anxiety-like behavior, and hippocampal cell proliferation in rats treated with a combination of doxorubicin and cyclophosphamide. Combined treatment with doxorubicin and cyclophosphamide produced cognitive impairment and anxiety-like behavior in rats. Nicotine treatment reversed the inhibition of novel location recognition induced by the combination treatment. This effect of nicotine was blocked by methyllycaconitine, a selective α7 nicotinic acetylcholine receptor (nAChR) antagonist, and dihydro-β-erythroidine, a selective α4β2 nAChR antagonist. In addition, nicotine normalized the amount of spontaneous alternation seen during the Y-maze task, which had been reduced by the combination treatment. This effect of nicotine was inhibited by dihydro-β-erythroidine. In comparison, nicotine did not affect the anxiety-like behavior induced by the combination treatment. Furthermore, the combination treatment reduced the number of proliferating cells in the subgranular zone of the hippocampal dentate gyrus, and this was also prevented by nicotine. Finally, the combination of doxorubicin and cyclophosphamide significantly reduced hippocampal α7 nAChR mRNA expression. These results suggest that nicotine inhibits doxorubicin and cyclophosphamide-induced cognitive impairment via α7 nAChR and α4β2 nAChR, and also enhances hippocampal neurogenesis.

KW - Anxiety

KW - Cognitive impairment

KW - Cyclophosphamide

KW - Doxorubicin

KW - Neurogenesis

KW - Nicotine

UR - http://www.scopus.com/inward/record.url?scp=85008449863&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85008449863&partnerID=8YFLogxK

U2 - 10.1007/s00210-016-1338-z

DO - 10.1007/s00210-016-1338-z

M3 - Article

VL - 390

SP - 369

EP - 378

JO - Naunyn-Schmiedeberg's Archives of Pharmacology

JF - Naunyn-Schmiedeberg's Archives of Pharmacology

SN - 0028-1298

IS - 4

ER -