The Journal of Neuroscience, August 9, 2006, 26(32):8320-8331; doi:10.1523/JNEUROSCI.4988-05.2006
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Behavioral/Systems/Cognitive
Central and Medial Amygdaloid Brain-Derived Neurotrophic Factor Signaling Plays a Critical Role in Alcohol-Drinking and Anxiety-Like Behaviors
Subhash C. Pandey,1,2,3
Huaibo Zhang,1,3
Adip Roy,1,3 and
Kaushik Misra1,2,3
1Departments of Psychiatry and 2Cell Biology and Anatomy, University of Illinois at Chicago, and 3Jesse Brown VA Medical Center, Chicago, Illinois 60612
Correspondence should be addressed to Dr. Subhash C. Pandey, Department of Psychiatry, University of Illinois at Chicago, and Jesse Brown VA Medical Center, 820 South Damen Avenue (M/C 151), Chicago, IL 60612. Email: scpandey{at}uic.edu
Brain-derived neurotrophic factor (BDNF) is a member of the nerve growth factor family of neurotrophins and plays a vital role in synaptic plasticity. This study investigated the involvement of the amygdaloid BDNF system in molecular mechanisms underlying anxiety and alcohol-drinking behaviors. Male Sprague Dawley rats were cannulated targeting central amygdala (CeA), medial amygdala (MeA), or basolateral amygdala (BLA), and BDNF expression was manipulated using an antisense oligodeoxynucleotide (ODN) strategy. Anxiety-like and alcohol-drinking behaviors were measured after infusion of BDNF sense and antisense ODNs with or without BDNF coinfusion, using the elevated plus-maze test and two-bottle free-choice paradigm, respectively. Here we report that BDNF antisense ODN infusions into the CeA and MeA, but not BLA, provoked anxiety-like behaviors in rats, which were rescued by BDNF coinfusion. The levels of BDNF, p-ERK1/2 (phosphorylated extracellular signal-regulated kinases 1/2), and p-CREB (phosphorylated cAMP responsive-element binding protein) were decreased by BDNF antisense, but not by sense, ODN infusions, which were restored to normal after BDNF coinfusions. Furthermore, BDNF antisense ODN infusions into the CeA or MeA, but not into BLA, increased alcohol intake, which was attenuated by BDNF coinfusions. These novel results suggest that decreased BDNF levels in the CeA and MeA, but not in the BLA, are crucial in regulating alcohol-drinking and anxiety-like behaviors in rats.
Key words: BDNF; CREB; amygdala; anxiety; alcohol preference; alcohol addiction
Received Nov. 22, 2005;
revised July 3, 2006;
accepted July 5, 2006.
Correspondence should be addressed to Dr. Subhash C. Pandey, Department of Psychiatry, University of Illinois at Chicago, and Jesse Brown VA Medical Center, 820 South Damen Avenue (M/C 151), Chicago, IL 60612. Email: scpandey{at}uic.edu
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