Intrathecal cdk5 inhibitor, roscovitine, attenuates morphine antinociceptive tolerance in rats

Cheng Haung Wang; Tsung Hsing Lee; Yi Jung Tsai; Jong Kang Liu; Yann Jang Chen; Lin Cheng Yang; Cheng Yuan Lu

Intrathecal cdk5 inhibitor, roscovitine, attenuates morphine antinociceptive tolerance in rats

Cheng Haung Wang, Tsung Hsing Lee, Yi Jung Tsai, Jong Kang Liu, Yann Jang Chen, Lin Cheng Yang, Cheng Yuan Lu^*

^*Corresponding author for this work

Research output: Contribution to journal › Journal Article › peer-review

18 Scopus citations

Abstract

AIM: To investigate the effect of cyclin-dependent kinase 5 (Cdk5) inhibitor roscovitine on the morphine antinociceptive tolerance development in rats. METHODS: Tail-flick test as pain threshold measurement and intrathecal injection techniques were used. RESULTS: Intrathecal roscovitine infusion alone produced an antinociceptive effect. Tolerance was induced by continuous intrathecal infusion of morphine 5 μg/h for 5 d. Co-administration of intrathecal roscovitine 1 μg/h for 5 d enhanced the morphine antinociceptive effect in tolerant rats. It also caused a shift in the morphine antinociceptive dose Cresponse curve to the left when co-administered with morphine during tolerance induction, and caused a 67 % reduction in the increase in the ED ₅₀ of morphine (dose producing 50 % of the maximum response). CONCLUSION: Cdk5 modulation is involved in the antinociceptive tolerance of morphine. Intrathecal roscovitine administration could attenuate this tolerance development.

Original language	English
Pages (from-to)	1027-1030
Number of pages	4
Journal	Acta Pharmacologica Sinica
Volume	25
Issue number	8
State	Published - 08 2004
Externally published	Yes

Keywords

Cyclin-dependent kinase 5
Morphine
Roscovitine

Cite this

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title = "Intrathecal cdk5 inhibitor, roscovitine, attenuates morphine antinociceptive tolerance in rats",

abstract = "AIM: To investigate the effect of cyclin-dependent kinase 5 (Cdk5) inhibitor roscovitine on the morphine antinociceptive tolerance development in rats. METHODS: Tail-flick test as pain threshold measurement and intrathecal injection techniques were used. RESULTS: Intrathecal roscovitine infusion alone produced an antinociceptive effect. Tolerance was induced by continuous intrathecal infusion of morphine 5 μg/h for 5 d. Co-administration of intrathecal roscovitine 1 μg/h for 5 d enhanced the morphine antinociceptive effect in tolerant rats. It also caused a shift in the morphine antinociceptive dose Cresponse curve to the left when co-administered with morphine during tolerance induction, and caused a 67 % reduction in the increase in the ED 50 of morphine (dose producing 50 % of the maximum response). CONCLUSION: Cdk5 modulation is involved in the antinociceptive tolerance of morphine. Intrathecal roscovitine administration could attenuate this tolerance development.",

keywords = "Cyclin-dependent kinase 5, Morphine, Roscovitine",

author = "Wang, {Cheng Haung} and Lee, {Tsung Hsing} and Tsai, {Yi Jung} and Liu, {Jong Kang} and Chen, {Yann Jang} and Yang, {Lin Cheng} and Lu, {Cheng Yuan}",

year = "2004",

month = aug,

language = "英语",

volume = "25",

pages = "1027--1030",

journal = "Acta Pharmacologica Sinica",

issn = "1671-4083",

publisher = "Springer Nature",

number = "8",

}

TY - JOUR

T1 - Intrathecal cdk5 inhibitor, roscovitine, attenuates morphine antinociceptive tolerance in rats

AU - Wang, Cheng Haung

AU - Lee, Tsung Hsing

AU - Tsai, Yi Jung

AU - Liu, Jong Kang

AU - Chen, Yann Jang

AU - Yang, Lin Cheng

AU - Lu, Cheng Yuan

PY - 2004/8

Y1 - 2004/8

N2 - AIM: To investigate the effect of cyclin-dependent kinase 5 (Cdk5) inhibitor roscovitine on the morphine antinociceptive tolerance development in rats. METHODS: Tail-flick test as pain threshold measurement and intrathecal injection techniques were used. RESULTS: Intrathecal roscovitine infusion alone produced an antinociceptive effect. Tolerance was induced by continuous intrathecal infusion of morphine 5 μg/h for 5 d. Co-administration of intrathecal roscovitine 1 μg/h for 5 d enhanced the morphine antinociceptive effect in tolerant rats. It also caused a shift in the morphine antinociceptive dose Cresponse curve to the left when co-administered with morphine during tolerance induction, and caused a 67 % reduction in the increase in the ED 50 of morphine (dose producing 50 % of the maximum response). CONCLUSION: Cdk5 modulation is involved in the antinociceptive tolerance of morphine. Intrathecal roscovitine administration could attenuate this tolerance development.

AB - AIM: To investigate the effect of cyclin-dependent kinase 5 (Cdk5) inhibitor roscovitine on the morphine antinociceptive tolerance development in rats. METHODS: Tail-flick test as pain threshold measurement and intrathecal injection techniques were used. RESULTS: Intrathecal roscovitine infusion alone produced an antinociceptive effect. Tolerance was induced by continuous intrathecal infusion of morphine 5 μg/h for 5 d. Co-administration of intrathecal roscovitine 1 μg/h for 5 d enhanced the morphine antinociceptive effect in tolerant rats. It also caused a shift in the morphine antinociceptive dose Cresponse curve to the left when co-administered with morphine during tolerance induction, and caused a 67 % reduction in the increase in the ED 50 of morphine (dose producing 50 % of the maximum response). CONCLUSION: Cdk5 modulation is involved in the antinociceptive tolerance of morphine. Intrathecal roscovitine administration could attenuate this tolerance development.

KW - Cyclin-dependent kinase 5

KW - Morphine

KW - Roscovitine

UR - http://www.scopus.com/inward/record.url?scp=4043114819&partnerID=8YFLogxK

M3 - 文章

C2 - 15301735

AN - SCOPUS:4043114819

SN - 1671-4083

VL - 25

SP - 1027

EP - 1030

JO - Acta Pharmacologica Sinica

JF - Acta Pharmacologica Sinica

IS - 8

ER -

Intrathecal cdk5 inhibitor, roscovitine, attenuates morphine antinociceptive tolerance in rats

Abstract

Keywords

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