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A Procedure to Observe Context-induced Renewal of Pavlovian-conditioned Alcohol-seeking Behavior in Rats
Published on: September 19, 2014
Memantine attenuated alcohol withdrawal-induced anxiety-like behaviors through down-regulating NR1-CaMKII-ERK
Ji Yuanyuan1, Zhu Junyan2, DeJi Cuola1
1College of Forensic Science, School of Medicine, Xi'an Jiaotong University, No. 76, Yanta West Road, Xi'an, Shaanxi 710061, China.
Abstract:
Alcohol abuse and anxiety disorders often occur concurrently, but their underlying cellular mechanisms remain unclear. N-methyl-D-aspartic acid receptors (NMDARs) have recently received attention from those interested in the neurobiology of anxiety. A chronic alcohol exposure rat model (28 consecutive days of 20% alcohol intake and 6 h of withdrawal) was established. Here, we investigated the NMDAR1 (NR1), Ca2+/calmodulin-dependent protein kinase II (CaMKII) and extracellular signal-regulated kinases (ERK) pathway in the modulation of anxiety-like behaviors in rats exposed to an open field and elevated plus maze (EPM) through systematic injections of memantine (a NMDAR inhibitor). We found that the NR1-CaMKII-ERK signaling pathway was activated after alcohol withdrawal in medial prefrontal cortex (mPFC) and nucleus accumbens shell (NAcSh) but not core (NAcC). Memantine treatment greatly ameliorated anxiety-like behavior in the rats experiencing alcohol withdrawal. Moreover, memantine uniformly suppressed the phosphorylation of NR1-CaMKII-ERK pathway induced by alcohol withdrawal. Our results suggest that activation of the NR1-CaMKII-ERK pathway in the mPFC and NAcSh is an important contributor to the molecular mechanisms underlying alcohol withdrawal-induced anxiety behaviors. NMDAR signaling pathway inhibitors are thus potential therapeutics for treating alcohol abuse.
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