Brandon G Oberlin1,2,3,4, Mario Dzemidzic5,6, William J A Eiler5, Claire R Carron5, Christina M Soeurt5, Martin H Plawecki7, Nicholas J Grahame8, Sean J O'Connor7,9, David A Kareken7,5,10,6. 1. Department of Psychiatry, School of Medicine, Indiana University, 355 W. 16th Street (GH 4800), Indianapolis, IN, 46202, USA. boberlin@iupui.edu. 2. Department of Neurology, School of Medicine, Indiana University, Indianapolis, IN, USA. boberlin@iupui.edu. 3. Stark Neurosciences Institute, School of Medicine, Indiana University, Indianapolis, IN, USA. boberlin@iupui.edu. 4. Department of Psychology, Indiana University-Purdue University Indianapolis, Indianapolis, IN, USA. boberlin@iupui.edu. 5. Department of Neurology, School of Medicine, Indiana University, Indianapolis, IN, USA. 6. Department of Radiology and Imaging Sciences, School of Medicine, Indiana University, Indianapolis, IN, USA. 7. Department of Psychiatry, School of Medicine, Indiana University, 355 W. 16th Street (GH 4800), Indianapolis, IN, 46202, USA. 8. Department of Psychology, Indiana University-Purdue University Indianapolis, Indianapolis, IN, USA. 9. Roudebush Veteran's Administration Medical Center, Indianapolis, IN, USA. 10. Stark Neurosciences Institute, School of Medicine, Indiana University, Indianapolis, IN, USA.
Abstract
RATIONALE: Alcohol-associated stimuli capture attention, yet drinkers differ in the precise stimuli that become paired with intoxication. OBJECTIVES: Extending our prior work to examine the influence of alcoholism risk factors, we paired abstract visual stimuli with intravenous alcohol delivered covertly and examined brain responses to these Pavlovian-conditioned stimuli in fMRI when subjects were not intoxicated. METHODS: Sixty healthy drinkers performed task-irrelevant alcohol conditioning that presented geometric shapes as conditioned stimuli. Shapes were paired with a rapidly rising alcohol limb (conditioned stimulus; CS+) using intravenous alcohol infusion targeting a final peak breath alcohol concentration of 0.045 g/dL or saline (CS-) infusion at matched rates. On day 2, subjects performed monetary delay discounting outside the scanner to assess delay tolerance and then underwent event-related fMRI while performing the same task with CS+, CS-, and an irrelevant symbol. RESULTS: CS+ elicited stronger activation than CS- in frontoparietal executive/attention and orbitofrontal reward-associated networks. Risk factors including family history, recent drinking, sex, and age of drinking onset did not relate to the [CS+ > CS-] activation. Delay-tolerant choice and [CS+ > CS-] activation in right inferior parietal cortex were positively related. CONCLUSIONS: Networks governing executive attention and reward showed enhanced responses to stimuli experimentally paired with intoxication, with the right parietal cortex implicated in both alcohol cue pairing and intertemporal choice. While different from our previous study results in 14 men, we believe this paradigm in a large sample of male and female drinkers offers novel insights into Pavlovian processes less affected by idiosyncratic drug associations.
RATIONALE: Alcohol-associated stimuli capture attention, yet drinkers differ in the precise stimuli that become paired with intoxication. OBJECTIVES: Extending our prior work to examine the influence of alcoholism risk factors, we paired abstract visual stimuli with intravenous alcohol delivered covertly and examined brain responses to these Pavlovian-conditioned stimuli in fMRI when subjects were not intoxicated. METHODS: Sixty healthy drinkers performed task-irrelevant alcohol conditioning that presented geometric shapes as conditioned stimuli. Shapes were paired with a rapidly rising alcohol limb (conditioned stimulus; CS+) using intravenous alcohol infusion targeting a final peak breath alcohol concentration of 0.045 g/dL or saline (CS-) infusion at matched rates. On day 2, subjects performed monetary delay discounting outside the scanner to assess delay tolerance and then underwent event-related fMRI while performing the same task with CS+, CS-, and an irrelevant symbol. RESULTS:CS+ elicited stronger activation than CS- in frontoparietal executive/attention and orbitofrontal reward-associated networks. Risk factors including family history, recent drinking, sex, and age of drinking onset did not relate to the [CS+ > CS-] activation. Delay-tolerant choice and [CS+ > CS-] activation in right inferior parietal cortex were positively related. CONCLUSIONS: Networks governing executive attention and reward showed enhanced responses to stimuli experimentally paired with intoxication, with the right parietal cortex implicated in both alcohol cue pairing and intertemporal choice. While different from our previous study results in 14 men, we believe this paradigm in a large sample of male and female drinkers offers novel insights into Pavlovian processes less affected by idiosyncratic drug associations.
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Authors: O Mawlawi; D Martinez; M Slifstein; A Broft; R Chatterjee; D R Hwang; Y Huang; N Simpson; K Ngo; R Van Heertum; M Laruelle Journal: J Cereb Blood Flow Metab Date: 2001-09 Impact factor: 6.200
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