A Preliminary Investigation of the Effect of Acute Alcohol on Dopamine Transmission as Assessed by [ 11 C]-(+)-PHNO.

BACKGROUND: Previous positron emission tomography (PET) studies exploring the effect of acute alcohol on dopamine (DA) levels have yielded inconsistent results, with only some studies suggesting increased synaptic DA levels after an alcohol challenge. The D2 /D3 agonist radiotracer, [11 C]-(+)-propyl-hexahydro-naphtho-oxazin ([11 C]-(+)-PHNO), has greater sensitivity to synaptic DA fluctuation than previously used antagonist radiotracers and is in principle more suitable for imaging alcohol-induced changes in DA. Its high affinity for the D3 receptor also enables measuring changes in D3 -rich brain areas which have previously been unexplored. The aim of this study was to investigate whether alcohol reduces [11 C]-(+)-PHNO binding in the striatum and in D3 -rich extra-striatal areas.

METHODS: Eight healthy drinkers underwent 2 [11 C]-(+)-PHNO PET scans following alcohol and placebo in a randomized, single-blind, crossover design. [11 C]-(+)-PHNO binding in the striatum and in the extra-striatal regions were compared between the 2 scans.

RESULTS: Acute alcohol administration did not significantly reduce [11 C]-(+)-PHNO binding in either the limbic striatum (d = 0.64), associative striatum (d < 0.20), or the sensorimotor striatum (d < 0.15). Similarly, there were no changes in binding in the D3 -rich areas of the ventral pallidum (d = 0.53), substantia nigra (d < 0.15), or globus pallidus (d < 0.15). However, greater percent change in [11 C]-(+)-PHNO binding (ΔBPND ) between scans was related to lower blood alcohol levels.

CONCLUSIONS: Using the agonist radiotracer, [11 C]-(+)-PHNO, our preliminary findings suggest that alcohol is not associated with robust changes in tracer binding in striatal or extra-striatal regions. However, we found that changes in [11 C]-(+)-PHNO binding following alcohol are dependent on blood alcohol levels suggesting that increases in DA may occur at lower stimulating doses. The effect of lower doses of alcohol on DA warrants further investigation in a larger study.