Dopamine D4-like receptor elevation in schizophrenia: cloned D2 and D4 receptors cannot be discriminated by raclopride competition against [3H]nemonapride.
Three independent studies have found that the density of dopamine D4-like receptors is elevated in postmortem brain striata in schizophrenia. This elevation has been questioned by a fourth study that used a different method and failed to detect a biphasic component when raclopride was used to complete against the binding of 1 nM [3H]nemonapride to schizophrenia tissue. To test whether this competition method could distinguish between dopamine D2 and D4 receptors, the present study used mixtures of only these two cloned receptors, free of all other receptors. Using combinations of cloned dopamine D2 and D4 receptors, this competition method could not resolve these components up to a level of 48% D4 receptors. Thus, the objections raised by the findings of the fourth study, mentioned above, do not appear valid. Furthermore, the present results indicate that the data using such a competition method actually mask a manyfold marked elevation in the density of dopamine D4-like receptors in schizophrenia.
Seeman
P
P
Department of Pharmacology, University of Toronto, Ontario, Canada.
Van Tol
H H
HH
D000818:Animals; D001549:Benzamides / Q000378:metabolism*; D001667:Binding, Competitive; D018492:Dopamine Antagonists / Q000378:metabolism; D006801:Humans; D066298:In Vitro Techniques; D020891:Raclopride; D051381:Rats; D011954:Receptors, Dopamine / Q000378:metabolism*; D017448:Receptors, Dopamine D2 / Q000378:metabolism*; D011994:Recombinant Proteins; D012457:Salicylamides / Q000378:metabolism*; D012559:Schizophrenia / Q000378:metabolism*
D001549:Benzamides; D018492:Dopamine Antagonists; D011954:Receptors, Dopamine; D017448:Receptors, Dopamine D2; D011994:Recombinant Proteins; D012457:Salicylamides; D020891:Raclopride; C030265:nemonapride