A critical need remains to identify how the brain's reward system is altered by alcoholism risk. Our objective is to determine if drinking and familial alcoholism are related to the brain's associative sensory response to an intensely sweet taste- a primary reward repeatedly linked to animal and human drug use. The rationale for the approach is to allow examination of those who have yet to learn the relationship between alcohol cues and intoxication, or who are ethically precluded from drinking (e.g., abstinent alcoholics). Our central hypothesis is that associative sensory (BOLD fMRI) responses to an intensely sweet taste in posterior orbital cortex are associated with abusive drinking, alcohol self-administration (measured in the lab), and familial alcoholism.
Aim 1 : Test if abusive drinking and alcohol-related problems are associated with the magnitude of the posterior orbitofrontal response to a highly sweet gustatory stimulus. Hypothesis 1: (a) Heavy drinking subjects have larger orbitofrontal responses to a highly sweet sucrose solution than subjects who drink socially;(b) alcohol-related problems correlate positively with the orbitofrontal response.
Aim 2 : Determine if alcohol self-administration is related to the magnitude of the sweet taste response. Hypothesis 2: The magnitude of orbital responses to oral sucrose correlates positively with the preferred level of alcohol intoxication achieved in a validated laboratory paradigm of intravenous alcohol self-administration.
Aim 3 : Determine if a family history of alcoholism is related to the magnitude of the response to a sweet taste. Hypothesis 3: Subjects with a family history of alcoholism have larger orbitofrontal responses to sweet taste delivery than family history negative subjects.
Aim 4 : Compare the associations between alcoholism risks and responses to: a) sucrose and b) monetary rewards. Hypothesis 4a: Alcoholism risks are related more to the orbital sensory response to an intensely sweet taste than to responses provoked by monetary reward anticipation (ventral striatum) or receipt (medial prefrontal). Hypothesis 4b: Alcoholism risks comprise blunted ventral striatal responses to monetary reward anticipation, elevated medial prefrontal responses to monetary receipt, and elevated orbital sensory association responses to high-concentration sucrose. Exploratory Aim 5: Test for associations between ?-opioid receptor genotype and reward system responses to a sweet gustatory stimulus. Endogenous opioids mediate central responses to both sucrose and alcohol. Hypothesis 5: 'A'(common) allele homozygotes of the ?-opioid receptor gene (rs1799971) have lower responses to oral sucrose than 'G'allele carriers. Our proposed research advances NIAAA's goal of identifying physiological traits of endophenotypic alcoholism risk, and will validate a probe for many populations, irrespective of age or drinking history. In this way, we can obtain new insights into the cerebral risk pathways that lead to alcoholism.

Public Health Relevance

Our proposed research will identify how alcoholism risk is reflected by brain responses to an inherently rewarding stimulus, the preference for which correlates with inherited alcoholism risk. This research will help us understand how alcoholism risk affects brain function, which will lead a clearer understanding of the brain reward circuits that can be targeted in prevention and treatment.

Agency
National Institute of Health (NIH)
Institute
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
Type
Research Project (R01)
Project #
1R01AA022476-01A1
Application #
8693202
Study Section
Neural Basis of Psychopathology, Addictions and Sleep Disorders Study Section (NPAS)
Program Officer
Matochik, John A
Project Start
2014-06-20
Project End
2019-04-30
Budget Start
2014-06-20
Budget End
2015-04-30
Support Year
1
Fiscal Year
2014
Total Cost
$601,406
Indirect Cost
$183,966
Name
Indiana University-Purdue University at Indianapolis
Department
Neurology
Type
Schools of Medicine
DUNS #
603007902
City
Indianapolis
State
IN
Country
United States
Zip Code
46202