The Alcohol Research Center of The Scripps Research Institute (TSRI-ARC) proposes to continue its interdisciplinary program focused on the theme of the central nervous system effects of alcohol. For this renewal application, the TSRI-ARC will be a P60 consisting of 9 components plus an Educational Component. Four core components are proposed: Administrative, Animal Models/Biochemical Measures, Biochemical and Pilot. Five research components are proposed: Cellular Electrophysiology, Cellular Physiology, Neuroendocrinology, Neurochemistry, and Clinical Neurobehavioral. The overall hypothesis of the TSRI-ARC is that with chronic binge drinking, the brain """"""""reward"""""""" systems become tolerant to alcohol while central stress systems become activated and that as a result, the neuroadaptive changes associated with chronic drinking produce an evolving set of neurobehavioral symptoms that include hypohedonia, anxiety, hyperarousal, sleep disturbances, and negative affect, conceptualized as the """"""""dark side"""""""" of addiction. The subhypotheses for the present proposal are: (1) The transition from low levels of drinking (1-2 drinks within 2 hours in humans) to chronic binge drinking (4-5 drinks within 2 hours in humans) is driven by decreased activity of opioid peptide systems and endocannabinoid systems in """"""""reward circuits"""""""" in the frontal cortex, and nucleus accumbens (Specific Aim 1). (2) The transition from binge drinking to dependence is driven by compromised function in the reward systems and recruitment of a dysregulated central stress system, most notably driven by changes in CRF, glutamate, and endocannabinoids in the extended amygdala (Specific Aim 2). (3) A particularly vulnerable local human clinical population has a phenotype of alcoholism that displays this transition from bingeing to dependence in young adulthood, allowing us to translate our findings in animals to humans and humans to animals (Specific Aim 3). We believe the proposed innovative approaches for testing these hypotheses will provide valuable insight into novel approaches for treating and preventing alcoholism in the human population. The TSRI-ARC also supports the Center at Large, which includes: 13 ROIs, 6 UOIs, one T32 NIAAA training grant, two R37s, one R13, one RC1 award. Members of the Center at Large have access to the Cores of the TSRI-ARC, the INIA Cores and the TSRI NIAAA Training Grant in Neuropsychopharmacology. Training and information dissemination to the San Diego community will be effected by the training opportunities of the Center including an NIAAA training grant and the Education Component.
This Center proposes to continue its interdisciplinary program focused on the theme of the central nervous system's effects of alcohol. A particularly vulnerable local human clinical population has a phenotype of alcoholism that displays a transition from bingeing to dependence in young adulthood, allowing us to translate our findings in animals to humans and humans to animals. We believe this project will provide valuable insight into novel approaches for treating and preventing alcoholism in the human population.
|Somkuwar, Sucharita S; Fannon, McKenzie J; Staples, Miranda C et al. (2016) Alcohol dependence-induced regulation of the proliferation and survival of adult brain progenitors is associated with altered BDNF-TrkB signaling. Brain Struct Funct 221:4319-4335|
|Curran, H Valerie; Freeman, Tom P; Mokrysz, Claire et al. (2016) Keep off the grass? Cannabis, cognition and addiction. Nat Rev Neurosci 17:293-306|
|Ehlers, Cindy L; Kim, Corinne; Gilder, David A et al. (2016) Lifetime history of traumatic events in a young adult Mexican American sample: Relation to substance dependence, affective disorder, acculturation stress, and PTSD. J Psychiatr Res 83:79-85|
|Melroy-Greif, Whitney E; Wilhelmsen, Kirk C; Ehlers, Cindy L (2016) Genetic variation in FAAH is associated with cannabis use disorders in a young adult sample of Mexican Americans. Drug Alcohol Depend 166:249-53|
|Sobieraj, Jeffery C; Kim, Airee; Fannon, McKenzie J et al. (2016) Chronic wheel running-induced reduction of extinction and reinstatement of methamphetamine seeking in methamphetamine dependent rats is associated with reduced number of periaqueductal gray dopamine neurons. Brain Struct Funct 221:261-76|
|de Guglielmo, Giordano; Crawford, Elena; Kim, Sarah et al. (2016) Recruitment of a Neuronal Ensemble in the Central Nucleus of the Amygdala Is Required for Alcohol Dependence. J Neurosci 36:9446-53|
|Buczynski, Matthew W; Herman, Melissa A; Hsu, Ku-Lung et al. (2016) Diacylglycerol lipase disinhibits VTA dopamine neurons during chronic nicotine exposure. Proc Natl Acad Sci U S A 113:1086-91|
|Criado, JosÃ© R; Gilder, David A; Kalafut, Mary A et al. (2016) Cardiovascular disease risks in adult Native and MexicanÂ Americans with a history of alcohol use disorders: association with cardiovascular autonomic control. Clin Auton Res 26:87-95|
|Varodayan, Florence P; Soni, Neeraj; Bajo, Michal et al. (2016) Chronic ethanol exposure decreases CB1 receptor function at GABAergic synapses in the rat central amygdala. Addict Biol 21:788-801|
|Herman, Melissa Ann; Roberto, Marisa (2016) Cell-type-specific tonic GABA signaling in the rat central amygdala is selectively altered by acute and chronic ethanol. Addict Biol 21:72-86|
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