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

Title
Adenylyl cyclase-5 activity in the nucleus accumbens regulates anxiety-related behavior
Authors
Kim K.-S.Lee K.-W.Baek I.-S.Lim C.-M.Krishnan V.Lee J.-K.Nestler E.J.Han P.-L.
Ewha Authors
한평림
SCOPUS Author ID
한평림scopus
Issue Date
2008
Journal Title
Journal of Neurochemistry
ISSN
0022-3042JCR Link
Citation
vol. 107, no. 1, pp. 105 - 115
Indexed
SCI; SCIE; SCOPUS WOS scopus
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. © 2008 The Authors.
DOI
10.1111/j.1471-4159.2008.05592.x
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일반대학원 > 뇌·인지과학과 > Journal papers
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