title: Effects of catecholamine depletion on D2 receptor binding, mood, and attentiveness in humans: a replication study.
abstract: 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.
authors.affiliation: Kunin-Lunenfeld Applied Research Unit, Baycrest Centre for Geriatric Care, Posluns Building, 7th Floor, Room 762, 3560 Bathurst Street, Toronto, Ontario, Canada M6A 2E1. pverhoeff@klaru-baycrest.on.ca
authors.forename: Nicolaas P L G
authors.initials: NP
authors.lastname: Verhoeff
authors.forename: Bruce K
authors.initials: BK
authors.lastname: Christensen
authors.forename: Doug
authors.initials: D
authors.lastname: Hussey
authors.forename: Maggie
authors.initials: M
authors.lastname: Lee
authors.forename: George
authors.initials: G
authors.lastname: Papatheodorou
authors.forename: Lili
authors.initials: L
authors.lastname: Kopala
authors.forename: Qing
authors.initials: Q
authors.lastname: Rui
authors.forename: Robert B
authors.initials: RB
authors.lastname: Zipursky
authors.forename: Shitij
authors.initials: S
authors.lastname: Kapur
mesh_terms: D000328:Adult; D000339:Affect / Q000502:physiology*; D001288:Attention / Q000502:physiology*; D002395:Catecholamines / Q000502:physiology*; D018492:Dopamine Antagonists; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D006719:Homovanillic Acid / Q000097:blood; D006801:Humans; D008297:Male; D008734:Methoxyhydroxyphenylglycol / Q000097:blood; D011581:Psychological Tests; D011597:Psychomotor Performance / Q000502:physiology; D020891:Raclopride; D019275:Radiopharmaceuticals; D017448:Receptors, Dopamine D2 / Q000378:metabolism*; D014055:Tomography, Emission-Computed; D019805:alpha-Methyltyrosine / Q000494:pharmacology
chemical_list: D002395:Catecholamines; D018492:Dopamine Antagonists; D004791:Enzyme Inhibitors; D019275:Radiopharmaceuticals; D017448:Receptors, Dopamine D2; D020891:Raclopride; D008734:Methoxyhydroxyphenylglycol; D019805:alpha-Methyltyrosine; D006719:Homovanillic Acid