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 |
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The Rewarding and Anxiolytic Properties of Ethanol within the Central Nucleus of the Amygdala: Mediated by Genetic Background and Nociceptin
CP Knight, SR Hauser, RA Waeiss, AI Molosh, PL Johnson, WA Truitt, WJ McBride, RL Bell, A Shekhar, ZA Rodd |
The Journal of pharmacology and experimental therapeutics | 2020 |
Epigenetic Mechanisms Underlying Pathobiology of Alcohol Use Disorder
RS Dulman, GM Wandling, SC Pandey |
Current Pathobiology Reports | 2020 |
Role of mTOR‐regulated autophagy in spine pruning defects and memory impairments induced by binge‐like ethanol treatment in adolescent mice
M Pascual, R LópezHidalgo, S MontagudRomero, JR UreñaPeralta, M RodríguezArias, C Guerri |
Brain Pathology | 2020 |
Histone modifications, DNA methylation, and the epigenetic code of alcohol use disorder.
Bohnsack JP, Pandey SC |
International review of neurobiology | 2020 |