Clinical Trial: Exploring Regulation and Function of Dopamine D3 Receptors in Alcohol Use Disorders: A [11C]-(+)-PHNO Study

Study Status: Recruiting
Recruit Status: Recruiting
Study Type: Interventional

Official Title: Exploring Regulation and Function of Dopamine D3 Receptors in Alcohol Use Disorders: A [11C]-(+)-PHNO Study

Brief Summary: There is a need to better understand the mechanisms underlying alcohol use and dependence in order to advance the clinical treatment of alcohol dependence. Here, the investigators will use Positron Emission Tomography to determine if there is an up-regulation of D3 receptors in the brains of subjects with alcohol use disorders. The investigators will also investigate the relationship between D3 binding and major phenotypes associated with alcohol use disorders, namely: alcohol cue induced craving and motivation to self-administer alcohol in the laboratory.

Detailed Summary:

Alcohol dependence is a devastating illness with social and medical costs estimated to be 180 billion dollars annually in the US. In the clinical treatment of alcoholism, reducing alcohol consumption in heavy drinkers is a major clinical challenge. As such, there has been much emphasis in both clinical and preclinical research to identify the substrates that mediate craving, excessive drinking and addiction. Identifying the neurobiological mechanisms of alcohol dependence may lead to the development of new and better treatment strategies. Preclinical studies indicate that the D3 receptor is involved in alcohol-cue response and in the motivation to drink alcohol. However, there is currently no data available in human subjects exploring the relationship between D3 and those behavioral responses in subjects with alcohol use disorders.

Aim #1: To measure the [11C]-(+)-PHNO PET binding levels in the brains of subjects with alcohol use disorders.

Aim #2: To determine the relationship between D3 receptor binding and alcohol cue induced craving and motivation to self-administer alcohol in the laboratory.

To achieve designated goals, the investigators will recruit 25 male and female subjects who are non-treatment seekers. After a period of abstinence from alcohol, participants will come to the Centre for Addiction of Mental Health for a [11C]-(+)-PHNO PET scan. Participants will also have additional sessions during which other alcohol-related measures will be assessed (i.e. alcohol cue induced craving and motivation to self-administer alcohol in the laboratory).

Current Primary Outcome: Dopamine D2/D3 receptor occupancy [ Time Frame: One PET scan after 2-7 days of abstinence from alcohol; ~2 hours in duration. ]

Original Primary Outcome: Same as current

Current Secondary Outcome:

• Alcohol craving ratings [ Time Frame: Cue paradigm session is expected to take ~1 hour and will occur on the PET day. ]
  Participants' ratings for alcohol craving acquired during the validated Cue-Induced Craving Paradigm (using the Alcohol Urge Questionnaire: 8 items on a 11-point Likert scale) will be correlated to dopamine receptor occupancy (outcome 1).
• Effort to obtain alcohol [ Time Frame: Single self-administration session will occur on its own day with a time commitment of ~6 hours. ]
  Laboratory alcohol self-administration paradigm in which participants press a button to intravenously self-administer small doses of alcohol will be used to assess amount of effort expended to obtain alcohol ("break point"). The # of button presses required to obtain the alcohol will increase as per the Progressive Ratio schedule. Regression analysis between effort and [11C]-(+)-PHNO binding (outcome 1) will be applied.

Original Secondary Outcome: Same as current

Information By: Centre for Addiction and Mental Health

Dates:
Date Received: January 16, 2017
Date Started: December 2016
Date Completion: December 2018
Last Updated: January 27, 2017
Last Verified: January 2017