Newdetection ofbraindopamine receptors with(3H)dihydroergocryptine (neuroleptics/ergots/neurotransmitters/norepinephrine/schizophrenia)

Because dihydroergocryptine (DHE)and closely related ergots aredopamine-mimetic agonists, wetested (3H)DHE asapossible ligand for(3H~dopamine receptors inthe calf caudate. Inorder toavoid (3HJDHE fromtagging a-ad- renergic receptors, anexcess of500nMphentolamine wasused toblock these sites, permitting thedopamine receptors tobe measured separately. Specific binding of(3H1DHE wasdefined astotal binding minusthat occurring inthepresence of1jMseeref. 12on (3H)ergotamine). Furthermore, Caron etal. (13, 14)have used (3H)DHE asaspecific dopamine ligand inrat pituitary tissue. Thus, because (3H)DHE canbindtomanytypes ofneuro- transmitter sites, previous results obtained byusing (3H)DHE onbrain tissue (8-11) aredifficult tointerpret. Caron etal.(13, 14)havefound that DHE acts asapure dopamine-like agonist onpituitary cells inculture. Itisalso knownthat 2-bromocryptine, which ischemically similar to DHE,hasdopamine-like agonist activity onratbehavior (15), mimicks theeffect ofL-3,4-dihydroxyphenylalanine onpatients with Parkinson disease (16), andreduces prolactin secretion in patients inafashion similar toother dopamine-mimetic drugs (17). These previous studies ontheergot compounds (13-17) in- dicate that itshould bepossible touse(3H)DHE asaligand for dopamine receptors inthebrain, providing theright conditions canbeestablished. Because thepituitary contains primarily dopamine receptors andfewifanynoradrenaline receptors, (3H)DHE specifically binds tothose sites (13, 14). Inorder to use(3H)DHE tolabel dopamine receptors inbrain tissue, however, itwould first benecessary toblock theadrenergic receptors. Thepresent study indicates that this ispossible. With Thecosts ofpublication ofthis article weredefrayed inpart bythe payment ofpage charges. This article musttherefore behereby marked "advertisement" inaccordance with 18U.S.C.§1734 solely toindicate this fact. excess phentolamine toblock thea-adrenergic brain receptors, thebinding of(3H)DHE exhibits all theproperties expected of aligand fordopamine receptors. Furthermore, thedisplace- mentof(3H)DHE bydopamine ornorepinephrine reveals in vitro evidence fortwotypes ofdopamine receptors.