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

doi:10.1016/j.drugalcdep.2009.05.015

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

Neuroscience

Producción científica: Article › revisión exhaustiva

8 Citas (Scopus)

Resumen

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.

Idioma original	English
Páginas (desde-hasta)	175-184
Número de páginas	10
Publicación	Drug and Alcohol Dependence
Volumen	104
N.º	1-2
DOI	https://doi.org/10.1016/j.drugalcdep.2009.05.015
Estado	Published - sept 1 2009

Nota bibliográfica

Funding Information:
This study was supported by a grant (2009K001253) from the Brain Research Center from 21st Century Frontier Research Program funded by the Ministry of Science and Technology, Republic of Korea, by a grant from Academic Frontier Project for Private Universities (2007–2011) from the Ministry of Education, Culture, Sports, Science and Technology of Japan, and by a grant of the Korea–Japan Joint Research Program (F01-2007-000-10165-0), Korea Science and Engineering Foundation (KOSEF). Kyo Hwan Koo was supported by BK 21 program. The funding sources had no further role in study design; in the collection, analysis and interpretation of data; in the writing of the report; or in the decision to submit the paper for publication.

Financiación

This study was supported by a grant (2009K001253) from the Brain Research Center from 21st Century Frontier Research Program funded by the Ministry of Science and Technology, Republic of Korea, by a grant from Academic Frontier Project for Private Universities (2007–2011) from the Ministry of Education, Culture, Sports, Science and Technology of Japan, and by a grant of the Korea–Japan Joint Research Program (F01-2007-000-10165-0), Korea Science and Engineering Foundation (KOSEF). Kyo Hwan Koo was supported by BK 21 program. The funding sources had no further role in study design; in the collection, analysis and interpretation of data; in the writing of the report; or in the decision to submit the paper for publication.

Financiadores	Número del financiador
Academic Frontier Project for Private Universities
Ministry of Education, Culture, Sports, Science and Technology	F01-2007-000-10165-0
Korea Science and Engineering Foundation
Ministry of Science and Technology, Croatia

ODS de las Naciones Unidas

Este resultado contribuye a los siguientes Objetivos de Desarrollo Sostenible

Good health and well being

ASJC Scopus subject areas

Toxicology
Pharmacology
Psychiatry and Mental health
Pharmacology (medical)

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10.1016/j.drugalcdep.2009.05.015

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title = "Prodynorphin gene deficiency potentiates nalbuphine-induced behavioral sensitization and withdrawal syndrome in mice",

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.",

keywords = "In vivo microdialysis, Nalbuphine, Prodynorphin gene knock-out mouse, Rewarding, Withdrawal signs",

author = "Shin, \{Eun Joo\} and Jang, \{Choon Gon\} and Guoying Bing and Park, \{Dae Hun\} and Oh, \{Chang Hyun\} and Koo, \{Kyo Hwan\} and Oh, \{Ki Wan\} and Kiyofumi Yamada and Toshitaka Nabeshima and Kim, \{Hyoung Chun\}",

note = "Funding Information: This study was supported by a grant (2009K001253) from the Brain Research Center from 21st Century Frontier Research Program funded by the Ministry of Science and Technology, Republic of Korea, by a grant from Academic Frontier Project for Private Universities (2007–2011) from the Ministry of Education, Culture, Sports, Science and Technology of Japan, and by a grant of the Korea–Japan Joint Research Program (F01-2007-000-10165-0), Korea Science and Engineering Foundation (KOSEF). Kyo Hwan Koo was supported by BK 21 program. The funding sources had no further role in study design; in the collection, analysis and interpretation of data; in the writing of the report; or in the decision to submit the paper for publication. ",

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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

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PY - 2009/9/1

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N2 - 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.

AB - 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.

KW - In vivo microdialysis

KW - Nalbuphine

KW - Prodynorphin gene knock-out mouse

KW - Rewarding

KW - Withdrawal signs

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

Resumen

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Financiación

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ASJC Scopus subject areas

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