Adenylyl cyclase-5 activity in the nucleus accumbens regulates anxiety-related behavior

Kyoung Shim Kim; Ko Woon Lee; In Sun Baek; Chae Moon Lim; Vaishnav Krishnan; Ja Kyeong Lee; Eric J. Nestler; Pyung Lim Han

doi:10.1111/j.1471-4159.2008.05592.x

Adenylyl cyclase-5 activity in the nucleus accumbens regulates anxiety-related behavior

Kyoung Shim Kim, Ko Woon Lee, In Sun Baek, Chae Moon Lim, Vaishnav Krishnan, Ja Kyeong Lee, Eric J. Nestler, Pyung Lim Han

Divison of Brain & Cognitive Sciences

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

61 Scopus citations

Abstract

Type 5 adenylyl cyclase (AC5) is highly concentrated in the dorsal striatum and nucleus accumbens (NAc), two brain areas which have been implicated in motor function, reward, and emotion. Here we demonstrate that mice lacking AC5 (AC5-/-) display strong reductions in anxiety-like behavior in several paradigms. This anxiolytic behavior in AC5-/- mice was reduced by the D ₁ receptor antagonist SCH23390 and enhanced by the D₁ dopamine receptor agonist, dihydrexidine (DHX). DHX-stimulated c-fos induction in AC5-/- mice was blunted in the dorso-lateral striatum, but it was overactivated in the dorso-medial striatum and NAc. The siRNA-mediated inhibition of AC5 levels within the NAc was sufficient to produce an anxiolytic-like response. Microarray and RT-PCR analyses revealed an up-regulation of prodynorphin and down-regulation of cholecystokinin (CCK) in the NAc of AC5-/- mice. Administration of nor-binaltorphimine (a kappa opioid receptor antagonist) or CCK-8s (a CCK receptor agonist) reversed the anxiolytic-like behavior exhibited by AC5-/- mutants. Taken together, these results suggest an essential role of AC5 in the NAc for maintaining normal levels of anxiety.

Original language	English
Pages (from-to)	105-115
Number of pages	11
Journal	Journal of Neurochemistry
Volume	107
Issue number	1
DOIs	https://doi.org/10.1111/j.1471-4159.2008.05592.x
State	Published - Oct 2008

Keywords

Anxiety
Dopamine receptor
Striatum
Type 5 adenylyl cyclase

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title = "Adenylyl cyclase-5 activity in the nucleus accumbens regulates anxiety-related behavior",

abstract = "Type 5 adenylyl cyclase (AC5) is highly concentrated in the dorsal striatum and nucleus accumbens (NAc), two brain areas which have been implicated in motor function, reward, and emotion. Here we demonstrate that mice lacking AC5 (AC5-/-) display strong reductions in anxiety-like behavior in several paradigms. This anxiolytic behavior in AC5-/- mice was reduced by the D 1 receptor antagonist SCH23390 and enhanced by the D1 dopamine receptor agonist, dihydrexidine (DHX). DHX-stimulated c-fos induction in AC5-/- mice was blunted in the dorso-lateral striatum, but it was overactivated in the dorso-medial striatum and NAc. The siRNA-mediated inhibition of AC5 levels within the NAc was sufficient to produce an anxiolytic-like response. Microarray and RT-PCR analyses revealed an up-regulation of prodynorphin and down-regulation of cholecystokinin (CCK) in the NAc of AC5-/- mice. Administration of nor-binaltorphimine (a kappa opioid receptor antagonist) or CCK-8s (a CCK receptor agonist) reversed the anxiolytic-like behavior exhibited by AC5-/- mutants. Taken together, these results suggest an essential role of AC5 in the NAc for maintaining normal levels of anxiety.",

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author = "Kim, {Kyoung Shim} and Lee, {Ko Woon} and Baek, {In Sun} and Lim, {Chae Moon} and Vaishnav Krishnan and Lee, {Ja Kyeong} and Nestler, {Eric J.} and Han, {Pyung Lim}",

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AU - Krishnan, Vaishnav

AU - Lee, Ja Kyeong

AU - Nestler, Eric J.

AU - Han, Pyung Lim

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AB - Type 5 adenylyl cyclase (AC5) is highly concentrated in the dorsal striatum and nucleus accumbens (NAc), two brain areas which have been implicated in motor function, reward, and emotion. Here we demonstrate that mice lacking AC5 (AC5-/-) display strong reductions in anxiety-like behavior in several paradigms. This anxiolytic behavior in AC5-/- mice was reduced by the D 1 receptor antagonist SCH23390 and enhanced by the D1 dopamine receptor agonist, dihydrexidine (DHX). DHX-stimulated c-fos induction in AC5-/- mice was blunted in the dorso-lateral striatum, but it was overactivated in the dorso-medial striatum and NAc. The siRNA-mediated inhibition of AC5 levels within the NAc was sufficient to produce an anxiolytic-like response. Microarray and RT-PCR analyses revealed an up-regulation of prodynorphin and down-regulation of cholecystokinin (CCK) in the NAc of AC5-/- mice. Administration of nor-binaltorphimine (a kappa opioid receptor antagonist) or CCK-8s (a CCK receptor agonist) reversed the anxiolytic-like behavior exhibited by AC5-/- mutants. Taken together, these results suggest an essential role of AC5 in the NAc for maintaining normal levels of anxiety.

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Adenylyl cyclase-5 activity in the nucleus accumbens regulates anxiety-related behavior

Abstract

Keywords

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