title: Dynamic, adaptive changes in MAO-A binding after alterations in substrate availability: an in vivo [(11)C]-harmine positron emission tomography study.
abstract: Monoamine oxidase A (MAO-A) is an important target in the pathophysiology and therapeutics of major depressive disorder, aggression, and neurodegenerative conditions. We measured the effect of changes in MAO-A substrate on MAO-A binding in regions implicated in affective and neurodegenerative disease with [(11)C]-harmine positron emission tomography in healthy volunteers. Monoamine oxidase A V(T), an index of MAO-A density, was decreased (mean: 14%±9%) following tryptophan depletion in prefrontal cortex (P<0.031), and elevated (mean: 17%±11%) in striatum following carbidopa-levodopa administration (P<0.007). These findings suggest an adaptive role for MAO-A in maintaining monoamine neurotransmitter homeostasis by rapidly compensating fluctuating monoamine levels.
authors.affiliation: Vivian M Rakoff PET Imaging Centre, Toronto, Canada.
authors.forename: Julia
authors.initials: J
authors.lastname: Sacher
authors.forename: Eugenii A
authors.initials: EA
authors.lastname: Rabiner
authors.forename: Michael
authors.initials: M
authors.lastname: Clark
authors.forename: Pablo
authors.initials: P
authors.lastname: Rusjan
authors.forename: Alexandra
authors.initials: A
authors.lastname: Soliman
authors.forename: Rada
authors.initials: R
authors.lastname: Boskovic
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Kish
authors.forename: Alan A
authors.initials: AA
authors.lastname: Wilson
authors.forename: Sylvain
authors.initials: S
authors.lastname: Houle
authors.forename: Jeffrey H
authors.initials: JH
authors.lastname: Meyer
mesh_terms: D002230:Carbidopa / Q000008:administration & dosage / Q000097:blood / Q000494:pharmacology; D002250:Carbon Radioisotopes; D003342:Corpus Striatum / Q000201:enzymology* / Q000378:metabolism; D004298:Dopamine / Q000378:metabolism; D018491:Dopamine Agonists / Q000008:administration & dosage / Q000097:blood / Q000494:pharmacology; D004338:Drug Combinations; D006247:Harmine / Q000378:metabolism*; D006801:Humans; D007980:Levodopa / Q000008:administration & dosage / Q000097:blood / Q000494:pharmacology; D008995:Monoamine Oxidase / Q000378:metabolism*; D010300:Parkinson Disease / Q000201:enzymology; D049268:Positron-Emission Tomography; D017397:Prefrontal Cortex / Q000201:enzymology* / Q000378:metabolism; D011485:Protein Binding; D012701:Serotonin / Q000378:metabolism; D013379:Substrate Specificity; D013997:Time Factors; D014364:Tryptophan / Q000097:blood
chemical_list: D002250:Carbon Radioisotopes; D018491:Dopamine Agonists; D004338:Drug Combinations; C009265:carbidopa, levodopa drug combination; D012701:Serotonin; D007980:Levodopa; D006247:Harmine; D014364:Tryptophan; D008995:Monoamine Oxidase; D002230:Carbidopa; D004298:Dopamine