title: Imaging extrastriatal dopamine D(2) receptor occupancy by endogenous dopamine in healthy humans.
abstract: The effect of endogenous dopamine on in vivo measurement of dopamine D(2) receptors in extrastriatal regions (thalamus and temporal cortex) was evaluated with single photon emission computed tomography and the high affinity ligand [123I]epidepride by comparing the binding potential before and after acute dopamine depletion. Dopamine depletion was achieved by per-oral administration of 5.5 g/70 kg body weight alpha-methyl-para-tyrosine given in 37 h. The alpha-methyl-para-tyrosine treatment increased the binding potential significantly in the temporal cortex (13+/-15%, P=0.036) but not in the thalamus (2+/-9%). The increase of the binding potential in the temporal cortex correlated strongly with the increase of dysphoric mood evaluated by the Positive and Negative Symptom Scale (PANSS) (rho=0.88, P=0.004). These results imply that [123I]epidepride, coupled with acute dopamine depletion might provide estimates of synaptic dopamine concentration.
authors.affiliation: Department of Psychiatry, Yale University, VA Connecticut, West Haven, CT 06516, USA. masahiro.fujita@yale.edu
authors.forename: M
authors.initials: M
authors.lastname: Fujita
authors.forename: N P
authors.initials: NP
authors.lastname: Verhoeff
authors.forename: A
authors.initials: A
authors.lastname: Varrone
authors.forename: S S
authors.initials: SS
authors.lastname: Zoghbi
authors.forename: R M
authors.initials: RM
authors.lastname: Baldwin
authors.forename: P A
authors.initials: PA
authors.lastname: Jatlow
authors.forename: G M
authors.initials: GM
authors.lastname: Anderson
authors.forename: J P
authors.initials: JP
authors.lastname: Seibyl
authors.forename: R B
authors.initials: RB
authors.lastname: Innis
mesh_terms: D000328:Adult; D001549:Benzamides / Q000378:metabolism; D001923:Brain Chemistry; D004298:Dopamine / Q000378:metabolism*; D005260:Female; D006719:Homovanillic Acid / Q000097:blood; D006801:Humans; D007457:Iodine Radioisotopes; D008140:Lorazepam / Q000494:pharmacology; D008297:Male; D008875:Middle Aged; D011759:Pyrrolidines / Q000378:metabolism; D017448:Receptors, Dopamine D2 / Q000032:analysis* / Q000378:metabolism; D015899:Tomography, Emission-Computed, Single-Photon; D019805:alpha-Methyltyrosine / Q000097:blood / Q000494:pharmacology
chemical_list: D001549:Benzamides; D007457:Iodine Radioisotopes; D011759:Pyrrolidines; D017448:Receptors, Dopamine D2; C063525:epidepride; D019805:alpha-Methyltyrosine; C055743:3-iodo-2-hydroxy-6-methoxy-N-((1-ethyl-2-pyrrolidinyl)methyl)benzamide; D008140:Lorazepam; D004298:Dopamine; D006719:Homovanillic Acid