Dopamine Release in the Human Brain Following Alcohol Administration

Imaging Alcohol Induced Dopamine Release in the Human Brain: a PET/11CPHNO Study

The purpose of this study is to examine whether there is an increase in dopamine levels in the human striatum following an oral administration of alcohol, as has been evidenced in animal models. This will be a Positron Emission Tomography (PET) study using the radiotracer, [11C]-(+)-PHNO (11C]-( + )-4-propyl- 3,4,4a,5,6,10b-hexahydro-2H-naphtho[1,2-b][1,4]oxazin-9-ol).

This will be a within subjects study in 8 heavy drinkers ages 21-45. The within factors will be PET scans following an alcoholic beverage and following a non-alcoholic beverage. Participants will also have a baseline session prior to the scans where they will complete various cognitive tasks and questionnaires. During each PET scan, subjective drug effects as well as heart rate, blood pressure, blood alcohol content and cortisol levels will be collected. The change in PHNO binding potential between the two scan conditions will be the primary outcome measure.

Inclusion Criteria:

• Healthy males and females of any ethnic origin between 21 and 45 years old.
• Reported consumption of at least two heavy drinking episodes (according to the National Institute on Alcohol Abuse and Alcoholism (NIAAA) criterion of 5 drinks for males or 4 for females) in the past 30 days prior to assessment.
• Willing and capable to provide written informed consent
• Good command of the English language

Exclusion Criteria:

• Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) diagnosis of alcohol dependence; receiving treatment for alcohol dependence
• Taking medications or have any medical condition for which alcohol is contraindicated
• Any medical condition requiring immediate investigation or treatment
• Previous head trauma/neurological condition such as clinically significant history of seizure disorder, a history of clinically significant head trauma (i.e., concussion resulting in clinically significant loss of consciousness) or past intracranial surgery
• Beck Depression Inventory score >16
• Current active or past suicidal ideation
• Pregnancy tested by urine and blood screen each PET study day or lactation
• Current DSM-IV diagnosis of any Axis I psychiatric disorder
• Regular use of any therapeutic or recreational psychoactive drug use during the last three months (with the exception of nicotine and alcohol) or other substance use disorder (including nicotine)
• Abnormal body mass (as defined as not within 20% of normal body mass index).
• Current past or anticipated exposure to radiation exceeding 20 mSv in the last year.
• Metal implants or paramagnetic objects within the body which may interfere with the magnetic resonance imaging (MRI).
• Claustrophobia or a history of panic attacks
• Abnormal clinical laboratory findings including serum creatinine greater than 2.0 mg/dl, abnormal liver function tests, elevated serum bilirubin (more than 1.5 times upper limit of normal), or pre-trial electrocardiogram (EKG) results demonstrating clinical significant abnormality