Investigating the effects of norepinephrine α1 receptor blockade on dopamine levels: A pilot PET study with [¹¹C]-(+)-PHNO in controls

Interest in a role for norepinephrine (NE) in substance use disorders has increased over recent years. In particular, its interaction with dopamine (DA) is of importance. In this study, positron emission tomography (PET) was used to explore the impact of prazosin (an alpha 1 NE antagonist) on DA levels. Healthy volunteers were administered prazosin for approximately 4 weeks at the daily dose of 15 mg to reach steady state. Participants were scanned with PET imaging and the [¹¹C]-(+)-PHNO tracer at baseline (before prazosin), at steady state, and after a wash out period. Prazosin administration was associated with an increase of [¹¹C]-(+)-PHNO binding potential in the dorsal caudate relative to baseline, which corresponds to a decrease in DA levels. This study is the first to demonstrate interactions between DA and NE in healthy humans.