title: Distribution and properties of GABA(B) antagonist [3H]CGP 62349 binding in the rhesus monkey thalamus and basal ganglia and the influence of lesions in the reticular thalamic nucleus.
abstract: GABA(B) receptors are believed to be associated with the efferents of the nucleus reticularis thalami, which is implicated in the regulation of activity in the thalamocortical-corticothalamic circuit and plays a role in absence seizures. Yet, the distribution of GABA(B) receptors in the thalamus has only been studied in the rat, and there is no comparable information in primates. The potent GABA(B) receptor antagonist [3H]CGP 62349 was used to study the distribution and binding properties of the receptor in control monkeys and those with small ibotenic acid lesions in the anterodorsal segment of the nucleus reticularis thalami. Eight-micrometer-thick cryostat sections of the fresh frozen brains were incubated in the presence of varying concentrations of the ligand. Autoradiographs were analysed using a quantitative image analysis technique, and binding parameters were calculated for select thalamic nuclei as well as basal ganglia structures present in the same sections. The overall number of GABA(B) binding sites in the monkey thalamus and basal ganglia was several-fold higher than previously reported values for the rat. In the thalamus, the receptors were distributed rather uniformly and the binding densities and affinities were high (Bmax range of 245.5-437.9 fmol/ mg of tissue, Kd range of 0.136-0.604 nM). In the basal ganglia, the number of binding sites and the affinities were lower (Bmax range of 51.1-244.2 fmol/mg of tissue; K(d) range of 0.416-1.394 nM), and the differences between nuclei were more pronounced, with striatum and substantia nigra pars compacta displaying the highest binding densities. Seven days post-lesion, a 20-30% decrease in Bmax values (P < 0.05) was found in the nuclei receiving input from the lesioned nucleus reticularis thalami sector (the mediodorsal nucleus and densicellular and magnocellular parts of the ventral anterior nucleus) without changes in affinity. No significant changes were detected in any other structures. The results of the lesioning experiments suggest that a portion of thalamic GABA(B) receptors is in a presynaptic location on the nucleus reticularis thalami efferents. The overall distribution pattern in the thalamus also suggests a partial association of GABA(B) receptors with corticothalamic terminals presynaptically.
authors.affiliation: Department of Anatomy and Cell Biology, University of Iowa College of Medicine, Iowa City 52242, USA.
authors.forename: A V
authors.initials: AV
authors.lastname: Ambardekar
authors.forename: I A
authors.initials: IA
authors.lastname: Ilinsky
authors.forename: W
authors.initials: W
authors.lastname: Forestl
authors.forename: N G
authors.initials: NG
authors.lastname: Bowery
authors.forename: K
authors.initials: K
authors.lastname: Kultas-Ilinsky
mesh_terms: D000818:Animals; D020643:Anterior Thalamic Nuclei / Q000737:chemistry / Q000378:metabolism; D001345:Autoradiography; D001479:Basal Ganglia / Q000737:chemistry* / Q000378:metabolism; D001565:Benzoates / Q000378:metabolism / Q000494:pharmacology*; D001667:Binding, Competitive; D001923:Brain Chemistry; D002531:Cerebellum / Q000737:chemistry / Q000378:metabolism; D003714:Denervation; D018690:Excitatory Amino Acid Agonists; D005260:Female; D058788:GABA-B Receptor Antagonists; D005829:Geniculate Bodies / Q000737:chemistry / Q000378:metabolism; D019262:Habenula / Q000737:chemistry / Q000378:metabolism; D007051:Ibotenic Acid; D020647:Lateral Thalamic Nuclei / Q000737:chemistry / Q000378:metabolism; D008253:Macaca mulatta; D008297:Male; D020645:Mediodorsal Thalamic Nucleus / Q000737:chemistry / Q000378:metabolism; D009433:Neural Inhibition / Q000502:physiology; D009943:Organophosphorus Compounds / Q000378:metabolism / Q000494:pharmacology*; D017729:Presynaptic Terminals / Q000737:chemistry / Q000378:metabolism; D020649:Pulvinar / Q000737:chemistry / Q000378:metabolism; D018080:Receptors, GABA-B / Q000378:metabolism*; D013787:Thalamic Nuclei / Q000737:chemistry* / Q000378:metabolism; D014316:Tritium; D020651:Ventral Thalamic Nuclei / Q000737:chemistry / Q000378:metabolism
chemical_list: D001565:Benzoates; C114540:CGP 62349; D018690:Excitatory Amino Acid Agonists; D058788:GABA-B Receptor Antagonists; D009943:Organophosphorus Compounds; D018080:Receptors, GABA-B; D014316:Tritium; D007051:Ibotenic Acid