Distribution and properties of GABA(B) antagonist [H-3]CGP 62349 binding in the rhesus monkey thalamus and basal ganglia and the influence of lesionsin the reticular thalamic nucleus

GABA(B) receptors are believed to be associated with the efferents of the n ucleus reticularis thalami, which is implicated in the regulation of activi ty in the thalamocortical-corticothalamic circuit and plays a role in absen ce 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 pr imates. The potent GABA(B) receptor antagonist [H-3]CGP 62349 was used to s tudy the distribution and binding properties of the receptor in control mon keys and those with small ibotenic acid lesions in the anterodorsal segment of the nucleus reticularis thalami. Eight-micrometer-thick cryostat sectio ns of the fresh frozen brains were incubated in the presence of varying con centrations of the ligand. Autoradiographs were analysed using a quantitati ve image analysis technique, and binding parameters were calculated for sel ect thalamic nuclei as well as basal ganglia structures present in the same sections. The overall number of GABA(B) binding sites in the monkey thalam us and basal ganglia was several-fold higher than previously reported value s for the rat. In the thalamus, the receptors were distributed rather unifo rmly and the binding densities and affinities were high (B-max range of 245 .5-437.9 fmol/mg of tissue, K-d range of 0.136-0.604 nM). In the basal gang lia, the number of binding sites and the affinities were lower (B-max range of 51.1-244.2 fmol/mg of tissue; Kd range of 0.416-1.394 nM), and the diff erences between nuclei were more pronounced, with striatum and substantia n igra pars compacta displaying the highest binding densities. Seven days pos t-lesion, a 20-30% decrease in B-max values (P < 0.05) was found in the nuc lei receiving input from the lesioned nucleus reticularis thalami sector (t he mediodorsal nucleus and densicellular and magnocellular parts of the ven tral 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 su ggests a partial association of GABA(B) receptors with corticothalamic term inals presynaptically. (C) 1999 IBRO. Published by Elsevier Science Ltd.