Multiple benzodiazepine receptors in the human basal ganglia: a detailed pharmacological and anatomical study.
The pharmacological characteristics and anatomical distribution of benzodiazepine receptors in the striatum (dorsal striatum, comprising the caudate nucleus and putamen, and ventral striatum) and globus pallidus (dorsal pallidum, comprising the external and internal segments, and ventral pallidum) of the human basal ganglia were examined in twelve cases aged 4-71 years. The pharmacology of the receptors was studied using computerized, non-linear least-squares regression analysis of [3H]flunitrazepam displacement by flunitrazepam, CL218,872 and ethyl beta-carboline-3-carboxylate binding to membranes. The results showed that the dorsal striatum (caudate nucleus and putamen) contained higher concentrations of receptors than the dorsal pallidum (external and internal segments). The dorsal striatum contained equal numbers of sites with high affinity (Type I) and low affinity (Type II) for CL218,872 and ethyl beta-carboline-3-carboxylate whereas the globus pallidus contained sites with only high affinity (Type I) for these ligands. The anatomical localization of the benzodiazepine receptor subtypes (Type I and II) was studied using quantitative autoradiography following in vitro labelling of cryostat sections with [3H]flunitrazepam in the absence or presence of the discriminating ligand CL218,872. The autoradiograms showed that benzodiazepine receptors were distributed throughout all regions of the human striatum in a heterogeneous fashion, i.e. high-density patches of receptors were set against a background matrix of lower receptor densities. The highest densities of receptors were seen in the ventral striatum where the patches were particularly extensive and showed densities 56% higher than the receptor densities in the dorsal striatal patches. Quantitative analysis showed that the patches in all striatal regions contained mainly Type II receptors (83%-86%) whereas the matrix regions in the ventral and dorsal striatum contained different proportions of the receptor subtypes; Type I receptors predominated (60%) in the matrix of the ventral striatum and Type II receptors predominated (67%-71%) in the matrix of the dorsal striatum. By contrast, the autoradiograms showed that the globus pallidus contained considerably lower concentrations of receptors than the striatum. The highest density of receptors in the globus pallidus was present in the ventral pallidum with successively lower concentrations in the external (26% less) and internal (66% less) segments of the dorsal pallidum. In agreement with the membrane binding studies the receptors in the globus pallidus were mainly of the Type I variety.(ABSTRACT TRUNCATED AT 400 WORDS)
Faull
R L
RL
Department of Anatomy, School of Medicine, University of Auckland, New Zealand.
Villiger
J W
JW
D000293:Adolescent; D000328:Adult; D000368:Aged; D001345:Autoradiography; D001479:Basal Ganglia / Q000378:metabolism*; D001667:Binding, Competitive; D002243:Carbolines / Q000378:metabolism; D002421:Caudate Nucleus / Q000378:metabolism; D002648:Child; D002675:Child, Preschool; D005260:Female; D005445:Flunitrazepam / Q000378:metabolism; D005917:Globus Pallidus / Q000378:metabolism; D006801:Humans; D008297:Male; D008875:Middle Aged; D011699:Putamen / Q000378:metabolism; D011724:Pyridazines / Q000378:metabolism; D011963:Receptors, GABA-A / Q000378:metabolism*
D002243:Carbolines; D011724:Pyridazines; D011963:Receptors, GABA-A; D005445:Flunitrazepam; C021604:CL 218872; C024915:beta-carboline-3-carboxylic acid ethyl ester