期刊
BRAIN RESEARCH
卷 1489, 期 -, 页码 27-36出版社
ELSEVIER SCIENCE BV
DOI: 10.1016/j.brainres.2012.10.016
关键词
CaMKII alpha; Adenylyl cyclase type 5; BDNF; Dorsal striatum; LORR
资金
- National Research Foundation of Korea from the Ministry of Science and Technology, Republic of Korea [2012R1A2A1A03010177]
- Ewha Womans University [GT5]
- National Research Foundation of Korea [2012R1A2A1A03010177] Funding Source: Korea Institute of Science & Technology Information (KISTI), National Science & Technology Information Service (NTIS)
High-dose ethanol inflicts sedation and loss of righting reflex (LORA). 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-CaMKII alpha, phospho-CREB, and BDNF in the dorsal striatum. CaMKII alpha(+/-) 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-CaMKII alpha, 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, CaMKII alpha and BDNF within the dorsal striatum is important for regulating the duration of ethanol-induced LORR. (c) 2012 Elsevier B.V. All rights reserved.
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