Prodynorphin gene deficiency potentiates nalbuphine-induced behavioral sensitization and withdrawal syndrome in mice

Eun Joo Shin, Choon Gon Jang, Guoying Bing, Dae Hun Park, Chang Hyun Oh, Kyo Hwan Koo, Ki Wan Oh, Kiyofumi Yamada, Toshitaka Nabeshima, Hyoung Chun Kim

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

Dynorphin is the presumed endogenous ligand for the kappa-opioid receptor. The dynorphin gene may play a role in psychotropic agent-mediated behavioral changes via dopaminergic modulation. Therefore, in this study, possible involvement of the dynorphin gene in nalbuphine-mediated behavioral responses was examined using prodynorphin (Pdyn) gene knock-out (-/-) mice. Pdyn gene deficiency potentiates nalbuphine-induced behavioral sensitization of locomotor activity and accumbal c-Fos expression. Administration of nalbuphine induced a significant increase in the dialysate dopamine level in the nucleus accumbens. This increase was more pronounced in the Pdyn (-/-) mice than in the wild-type (WT) mice. In addition, Pdyn (-/-) mice were more vulnerable to the naloxone-precipitated withdrawal syndrome (i.e., teeth chattering, wet dog shakes, forepaw tremors, jumping, weight loss, and global withdrawal score) after repeated treatment with nalbuphine than the WT mice. Consistently, nor-binaltorphimine, a kappa-opioid receptor antagonist, significantly potentiated nalbuphine-induced behavioral effects in WT mice, whereas U-50488H, a kappa-opioid receptor agonist, significantly attenuated these changes in Pdyn (-/-) mice in a dose-dependent manner. Our data suggest that the kappa-opioid receptor/dynorphin system is specifically modulated in response to behavioral sensitization and withdrawal signs induced by nalbuphine.

Original languageEnglish
Pages (from-to)175-184
Number of pages10
JournalDrug and Alcohol Dependence
Volume104
Issue number1-2
DOIs
Publication statusPublished - 01-09-2009
Externally publishedYes

Fingerprint

Nalbuphine
Dynorphins
kappa Opioid Receptor
Genes
(trans)-Isomer 3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide
Gene Knockout Techniques
Narcotic Antagonists
Dialysis Solutions
Nucleus Accumbens
Tremor
Locomotion
Naloxone
Knockout Mice
preproenkephalin
Weight Loss
Dopamine
Tooth
Modulation
Dogs
Ligands

All Science Journal Classification (ASJC) codes

  • Toxicology
  • Pharmacology
  • Psychiatry and Mental health
  • Pharmacology (medical)

Cite this

Shin, Eun Joo ; Jang, Choon Gon ; Bing, Guoying ; Park, Dae Hun ; Oh, Chang Hyun ; Koo, Kyo Hwan ; Oh, Ki Wan ; Yamada, Kiyofumi ; Nabeshima, Toshitaka ; Kim, Hyoung Chun. / Prodynorphin gene deficiency potentiates nalbuphine-induced behavioral sensitization and withdrawal syndrome in mice. In: Drug and Alcohol Dependence. 2009 ; Vol. 104, No. 1-2. pp. 175-184.
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Prodynorphin gene deficiency potentiates nalbuphine-induced behavioral sensitization and withdrawal syndrome in mice. / Shin, Eun Joo; Jang, Choon Gon; Bing, Guoying; Park, Dae Hun; Oh, Chang Hyun; Koo, Kyo Hwan; Oh, Ki Wan; Yamada, Kiyofumi; Nabeshima, Toshitaka; Kim, Hyoung Chun.

In: Drug and Alcohol Dependence, Vol. 104, No. 1-2, 01.09.2009, p. 175-184.

Research output: Contribution to journalArticle

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T1 - Prodynorphin gene deficiency potentiates nalbuphine-induced behavioral sensitization and withdrawal syndrome in mice

AU - Shin, Eun Joo

AU - Jang, Choon Gon

AU - Bing, Guoying

AU - Park, Dae Hun

AU - Oh, Chang Hyun

AU - Koo, Kyo Hwan

AU - Oh, Ki Wan

AU - Yamada, Kiyofumi

AU - Nabeshima, Toshitaka

AU - Kim, Hyoung Chun

PY - 2009/9/1

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