We investigated the role of cAMP-responsive element–binding protein (CREB) in genetic predisposition to anxiety and alcohol-drinking behaviors using alcohol-preferring (P) and -nonpreferring (NP) rats. The levels of CREB, phosphorylated CREB, and neuropeptide Y (NPY) were innately lower in the central amygdala (CeA) and medial amygdala (MeA), but not in the basolateral amygdala (BLA), of P rats compared with NP rats. P rats displayed higher baseline anxiety-like behaviors and consumed higher amounts of alcohol compared with NP rats. Ethanol injection or voluntary intake reduced the higher anxiety levels in P rats. Ethanol also increased CREB function in the CeA and MeA, but not in the BLA, of P rats. Infusion of the PKA activator Sp-cAMP or NPY into the CeA decreased the alcohol intake and anxiety-like behaviors of P rats. PKA activator infusion also increased CREB function in the CeA of P rats. On the other hand, ethanol injection or voluntary intake did not produce any changes either in anxiety levels or on CREB function in the amygdaloid structures of NP rats. Interestingly, infusion of the PKA inhibitor Rp-cAMP into the CeA provoked anxiety-like behaviors and increased alcohol intake in NP rats. PKA inhibitor decreased CREB function in the CeA of NP rats. These novel results provide the first evidence to our knowledge that decreased CREB function in the CeA may be operative in maintaining the high anxiety and excessive alcohol-drinking behaviors of P rats.
Subhash C. Pandey, Huaibo Zhang, Adip Roy, Tiejun Xu
Title and authors | Publication | Year |
---|---|---|
Ethanol sensitivity: a central role for CREB transcription regulation in the cerebellum
GK Acquaah-Mensah, V Misra, S Biswal |
BMC Genomics | 2006 |
Loosening addiction's deadly grip. Recent research paints a picture of addiction as a progressive, chronic neurological disease that wreaks havoc with brain chemistry
V Brower |
EMBO reports | 2006 |
Central and Medial Amygdaloid Brain-Derived Neurotrophic Factor Signaling Plays a Critical Role in Alcohol-Drinking and Anxiety-Like Behaviors
SC Pandey, H Zhang, A Roy, K Misra |
The Journal of neuroscience : the official journal of the Society for Neuroscience | 2006 |