Neural and Neuroendocrine response to compulsive alcohol motivation

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ABSTRACT Compulsive alcohol motivation and loss of control alcohol intake are hallmark features of binge/heavy and chronic alcohol use but the mechanisms that drive this excessive alcohol consumption are not well studied. Excessive alcohol use leads to neuroendocrine adaptations in the hypothalamic-pituitary adrenal (HPA) axis and neural changes in the reward and motivation pathways which may lead to compulsive alcohol motivation and loss of control alcohol intake. In preliminary studies we find in binge/heavy (BH) relative to moderate non- binge (MD) social drinkers that altered stress and cue related cortisol responses and high subjective alcohol craving predicts compulsive alcohol motivation and intake in the alcohol taste test (ATT), used here as an implicit test of compulsive alcohol motivation and intake. Furthermore, high alcohol intake led to an increased and sensitized cortisol response and high alcohol craving only in the BH and not the MD group. Expanding on these results, we propose to develop a neuroimaging approach utilizing multiband, arterial spin labelling (ASL) measurement combined with simultaneous neuroendocrine and breath alcohol levels to test the hypothesis that high alcohol motivation and intake leads to increased cortisol responses and greater dorsal striatal blood flow which in turn predicts increased subjective craving and compulsive alcohol motivation and intake in binge/heavy (BH) relative to moderate (MD) social drinkers. Thirty-two MD and 32 BH socially drinking men and women (ages 21-45; equal gender) will be studied in a neuroimaging session to address the following specific aims: Specific Aim 1: To assess subjective and behavioral alcohol motivation and intake, CBF changes in the striatum and ventromedial prefrontal cortex (VmPFC), HPA axis and alpha-amylase response in the non-alcoholic and alcoholic beer taste test conditions in binge heavy and moderate SD groups. Specific Aim 2: To evaluate if alcohol amount and ascending breath alcohol levels predict increased cortisol and CBF response in the ventral and dorsal striatum in the BH compared to MD group. Specific Aim 3: To examine whether increased cortisol and striatal CBF and lower VmPFC CBF predict increased subjective craving and alcohol motivation and intake in post-scan alcohol taste test. Exploratory Aims: To explore sex differences in the above aims and also assess alcohol- and cortisol-related changes in brain connectivity in BH and MD groups. Using state-of-the-art neuroimaging technologies, this project promises to develop and validate a multimethod neural and neuroendocrine imaging protocol to assess whether alcohol-related glucocorticoid signaling plays a role in compulsive alcohol motivation. Successful completion of the aims could lead to new approaches for testing novel therapeutics in prevention and treatment of alcoholism.