Effects of catecholamine depletion on D2 receptor binding, mood, and attentiveness in humans: a replication study

The effect of catecholamine depletion, achieved by per-oral administration of 5250 mg alpha-methyl-para-tyrosine (AMPT) given in the 29 h prior to [11C]raclopride positron emission tomography (PET) was studied on measures of dopamine (DA) release, mood, and attention. Neostriatal DA levels in vivo were estimated by comparing the neostriatal DA D(2) receptor binding potential (D(2)RBP) before and after catecholamine depletion using PET and the radiotracer [11C]raclopride. Six healthy subjects completed the protocol. The AMPT treatment increased D(2)RBP significantly by 13.3+/-5.9% (average+/-standard deviation) and decreased plasma levels of the DA metabolite homovanillic acid (HVA) by 62+/-17%, and levels of the norepinephrine (NE) metabolite 3-methoxy-4-hydroxyphenethyleneglycol (MHPG) by 66+/-5%. Catecholamine depletion resulted in decreased happiness, euphoria, energy, talkativeness, vigor, and attentiveness, and in increased sleepiness, fatigue, sedation, and eye blink rate (EBR). These changes were not correlated with the D(2)RBP increments. The results of this study are overall consistent with previous findings by our group using the same methodology in a different cohort of six healthy subjects.