The dorsal striatum expressing adenylyl cyclase-5 controls behavioral sensitivity of the righting reflex to high-dose ethanol

Kyoung Shim Kim; Hannah Kim; Sun Kyu Park; Pyung Lim Han

doi:10.1016/j.brainres.2012.10.016

The dorsal striatum expressing adenylyl cyclase-5 controls behavioral sensitivity of the righting reflex to high-dose ethanol

Kyoung Shim Kim, Hannah Kim, Sun Kyu Park, Pyung Lim Han

Divison of Brain & Cognitive Sciences

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

10 Scopus citations

Abstract

High-dose ethanol inflicts sedation and loss of righting reflex (LORR). Recently, it was reported that AC5 knockout (AC5^-/-) mice consumed more ethanol and showed reduced sensitivity to high-dose ethanol compared to wild-type mice. As an extension of the previous study, in the present study we examined the signaling mechanism regulating altered behavioral sensitivity of LORR in AC5^-/- mice. AC5^-/- mice had enhanced phosphorylation of the NR2B subunit of NMDA receptors in the dorsal striatum and a partial reduction of MK801 (NMDA receptor antagonist)/ethanol-induced LORR. AC5^-/- mice showed increased levels of phospho-CaMKIIα, phospho-CREB, and BDNF in the dorsal striatum. CaMKIIα^+/- or BDNF^+/- mice displayed enhanced LORR, a behavioral phenotype opposite to that displayed by AC5^-/- mice. Consistently with these results, stereotaxic infusion of KN62 (CaMKII inhibitor), siRNA-CaMKIIα, or siRNA-BDNF, within the dorsal striatum was sufficient to prolong LORR. These results suggest that neural mechanism is important for regulating behavioral sensitivity of LORR and that the signaling pathway(s) interplayed by AC5, CaMKIIα and BDNF within the dorsal striatum is important for regulating the duration of ethanol-induced LORR.

Original language	English
Pages (from-to)	27-36
Number of pages	10
Journal	Brain Research
Volume	1489
DOIs	https://doi.org/10.1016/j.brainres.2012.10.016
State	Published - 13 Dec 2012

Bibliographical note

Funding Information:
This research was supported by a grant ( 2012R1A2A1A03010177 ) from the National Research Foundation of Korea from the Ministry of Science and Technology, Republic of Korea , and partly by an internal grant ( GT5 ) from Ewha Womans University .

Keywords

Adenylyl cyclase type 5
BDNF
CaMKIIα
Dorsal striatum
LORR

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10.1016/j.brainres.2012.10.016

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title = "The dorsal striatum expressing adenylyl cyclase-5 controls behavioral sensitivity of the righting reflex to high-dose ethanol",

abstract = "High-dose ethanol inflicts sedation and loss of righting reflex (LORR). Recently, it was reported that AC5 knockout (AC5-/-) mice consumed more ethanol and showed reduced sensitivity to high-dose ethanol compared to wild-type mice. As an extension of the previous study, in the present study we examined the signaling mechanism regulating altered behavioral sensitivity of LORR in AC5-/- mice. AC5-/- mice had enhanced phosphorylation of the NR2B subunit of NMDA receptors in the dorsal striatum and a partial reduction of MK801 (NMDA receptor antagonist)/ethanol-induced LORR. AC5-/- mice showed increased levels of phospho-CaMKIIα, phospho-CREB, and BDNF in the dorsal striatum. CaMKIIα+/- or BDNF+/- mice displayed enhanced LORR, a behavioral phenotype opposite to that displayed by AC5-/- mice. Consistently with these results, stereotaxic infusion of KN62 (CaMKII inhibitor), siRNA-CaMKIIα, or siRNA-BDNF, within the dorsal striatum was sufficient to prolong LORR. These results suggest that neural mechanism is important for regulating behavioral sensitivity of LORR and that the signaling pathway(s) interplayed by AC5, CaMKIIα and BDNF within the dorsal striatum is important for regulating the duration of ethanol-induced LORR.",

keywords = "Adenylyl cyclase type 5, BDNF, CaMKIIα, Dorsal striatum, LORR",

author = "Kim, {Kyoung Shim} and Hannah Kim and Park, {Sun Kyu} and Han, {Pyung Lim}",

note = "Funding Information: This research was supported by a grant ( 2012R1A2A1A03010177 ) from the National Research Foundation of Korea from the Ministry of Science and Technology, Republic of Korea , and partly by an internal grant ( GT5 ) from Ewha Womans University .",

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AU - Kim, Kyoung Shim

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AU - Park, Sun Kyu

AU - Han, Pyung Lim

N1 - Funding Information: This research was supported by a grant ( 2012R1A2A1A03010177 ) from the National Research Foundation of Korea from the Ministry of Science and Technology, Republic of Korea , and partly by an internal grant ( GT5 ) from Ewha Womans University .

PY - 2012/12/13

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N2 - High-dose ethanol inflicts sedation and loss of righting reflex (LORR). Recently, it was reported that AC5 knockout (AC5-/-) mice consumed more ethanol and showed reduced sensitivity to high-dose ethanol compared to wild-type mice. As an extension of the previous study, in the present study we examined the signaling mechanism regulating altered behavioral sensitivity of LORR in AC5-/- mice. AC5-/- mice had enhanced phosphorylation of the NR2B subunit of NMDA receptors in the dorsal striatum and a partial reduction of MK801 (NMDA receptor antagonist)/ethanol-induced LORR. AC5-/- mice showed increased levels of phospho-CaMKIIα, phospho-CREB, and BDNF in the dorsal striatum. CaMKIIα+/- or BDNF+/- mice displayed enhanced LORR, a behavioral phenotype opposite to that displayed by AC5-/- mice. Consistently with these results, stereotaxic infusion of KN62 (CaMKII inhibitor), siRNA-CaMKIIα, or siRNA-BDNF, within the dorsal striatum was sufficient to prolong LORR. These results suggest that neural mechanism is important for regulating behavioral sensitivity of LORR and that the signaling pathway(s) interplayed by AC5, CaMKIIα and BDNF within the dorsal striatum is important for regulating the duration of ethanol-induced LORR.

AB - High-dose ethanol inflicts sedation and loss of righting reflex (LORR). Recently, it was reported that AC5 knockout (AC5-/-) mice consumed more ethanol and showed reduced sensitivity to high-dose ethanol compared to wild-type mice. As an extension of the previous study, in the present study we examined the signaling mechanism regulating altered behavioral sensitivity of LORR in AC5-/- mice. AC5-/- mice had enhanced phosphorylation of the NR2B subunit of NMDA receptors in the dorsal striatum and a partial reduction of MK801 (NMDA receptor antagonist)/ethanol-induced LORR. AC5-/- mice showed increased levels of phospho-CaMKIIα, phospho-CREB, and BDNF in the dorsal striatum. CaMKIIα+/- or BDNF+/- mice displayed enhanced LORR, a behavioral phenotype opposite to that displayed by AC5-/- mice. Consistently with these results, stereotaxic infusion of KN62 (CaMKII inhibitor), siRNA-CaMKIIα, or siRNA-BDNF, within the dorsal striatum was sufficient to prolong LORR. These results suggest that neural mechanism is important for regulating behavioral sensitivity of LORR and that the signaling pathway(s) interplayed by AC5, CaMKIIα and BDNF within the dorsal striatum is important for regulating the duration of ethanol-induced LORR.

KW - Adenylyl cyclase type 5

KW - BDNF

KW - CaMKIIα

KW - Dorsal striatum

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ER -

The dorsal striatum expressing adenylyl cyclase-5 controls behavioral sensitivity of the righting reflex to high-dose ethanol

Abstract

Bibliographical note

Keywords

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