Low doses of alcohol substantially decrease glucose metabolism in the human brain.

Moderate doses of alcohol decrease glucose metabolism in the human brain, which has been interpreted to reflect alcohol-induced decreases in brain activity. Here, we measure the effects of two relatively low doses of alcohol (0.25 g/kg and 0.5 g/kg, or 5 to 10 mM in total body H2O) on glucose metabolism in the human brain. Twenty healthy control subjects were tested using positron emission tomography (PET) and FDG after placebo and after acute oral administration of either 0.25 g/kg, or 0.5 g/kg of alcohol, administered over 40 min. Both doses of alcohol significantly decreased whole-brain glucose metabolism (10% and 23% respectively). The responses differed between doses; whereas the 0.25 g/kg dose predominantly reduced metabolism in cortical regions, the 0.5 g/kg dose reduced metabolism in cortical as well as subcortical regions (i.e. cerebellum, mesencephalon, basal ganglia and thalamus). These doses of alcohol did not significantly change the scores in cognitive performance, which contrasts with our previous results showing that a 13% reduction in brain metabolism by lorazepam was associated with significant impairment in performance on the same battery of cognitive tests. This seemingly paradoxical finding raises the possibility that the large brain metabolic decrements during alcohol intoxication could reflect a shift in the substrate for energy utilization, particularly in light of new evidence that blood-borne acetate, which is markedly increased during intoxication, is a substrate for energy production by the brain.

Brain DA D2 receptors predict reinforcing effects of stimulants in humans: replication study.

We had shown that striatal DA D2 receptors levels predicted the reinforcing responses to the psychostimulant drug methylphenidate in nondrug-abusing subjects. Here, we assessed the replicability of this finding. We measured D2 receptors with PET and [(11)C]raclopride (twice to determine stability) in seven nondrug-abusing subjects to assess if they predicted the self-reports of "drug-liking" to intravenous methylphenidate (0.5 mg/kg). DA D2 measures were significantly correlated with "drug-liking" in both evaluations (r = 0.82 and r = 0.78); subjects with the lowest levels reported the higher ratings of "drug-liking" and vice versa. These results replicate our previous findings and provide further evidence that striatal DA D2 receptors modulate reinforcing responses to stimulants in humans and may underlie predisposition for drug self-administration.