Quantitative autoradiography of [3H]norharman [( 3H]beta-carboline) binding sites in the rat brain.
The anatomical distribution of [3H]norharman binding sites was determined by quantitative autoradiography in rat brain slices. They are enriched in hypothalamic, thalamic, accumbens and amygdaloid nuclei as well as in hippocampal, neocortical and olfactory-related structures. The distribution pattern differs from that of other previously described receptors or binding sites (e.g. monoamine oxidase, benzodiazepine, tryptamine, 5-hydroxytryptamine receptors (5-HT1A, 5-HT1B, 5-HT1C, 5HT2], which suggests that a unique class of [3H]norharman binding sites exists in the rat brain. The findings are consistent with previous experiments which showed high affinity binding sites for [3H]norharman in rat brain membranes (KD 1.552 nM; autoradiography KD 5.5 nM). A correspondence in the displacing activity of drugs was found for both methods (crude membrane fraction: harman much greater than tryptamine much greater than 5-hydroxytryptamine greater than N-methyl-beta-carboline-3-carboxamide (FG 7142) = diazepam; autoradiography: harman much greater than tryptamine much greater than FG 7142 greater than 5-hydroxytryptamine greater than diazepam). Provided that the binding sites represent functional receptors, the present anatomical findings may explain the biological effects of norharman, e. g. pro-conflict behaviour (limbic-hypothalamic structures), tonic-clonic convulsions (limbic-cortical structures) and alterations of locomotor activity (accumbens nucleus).
Pawlik
M
M
Department of Neuropsychopharmacology, Free University, Berlin, FRG.
Kaulen
P
P
Baumgarten
H G
HG
Rommelspacher
H
H
D000470:Alkaloids / Q000378:metabolism*; D000818:Animals; D001667:Binding, Competitive; D001921:Brain / Q000378:metabolism*; D002243:Carbolines; D005260:Female; D006247:Harmine / Q000031:analogs & derivatives / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D011963:Receptors, GABA-A / Q000378:metabolism*; D014363:Tryptamines / Q000378:metabolism
D000470:Alkaloids; D002243:Carbolines; D011963:Receptors, GABA-A; D014363:Tryptamines; C030820:tryptamine; D006247:Harmine; C005010:harman; C010262:norharman