Elsevier

Neuroscience

Volume 93, Issue 4, August 1999, Pages 1339-1347
Neuroscience

Distribution and properties of GABAB antagonist [3H]CGP 62349 binding in the rhesus monkey thalamus and basal ganglia and the influence of lesions in the reticular thalamic nucleus

https://doi.org/10.1016/S0306-4522(99)00282-1Get rights and content

Abstract

GABAB 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 GABAB receptors in the thalamus has only been studied in the rat, and there is no comparable information in primates. The potent GABAB 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 GABAB 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; Kd 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 GABAB 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 GABAB receptors with corticothalamic terminals presynaptically.

Section snippets

Experimental procedures

The study was performed on tissue from four adult rhesus monkeys (Macaca mulatta) of either sex weighing 4.9–6.0 kg. In two of them small ibotenic acid (Sigma, St Louis, MO, 10 μg/μl in saline) injections were made in the anterior pole of the NRT unilaterally, and the two others were used as controls.

Distribution and binding properties of [3H]CGP 62349 in control animals

Most of the nuclei studied in the thalamus and basal ganglia displayed saturable antagonist binding as demonstrated by binding curves (Fig. 1). The calculated Bmax and Kd values for each nucleus and structure of interest and are summarized in Table 1. The results demonstrate that the density of the [3H]CGP 62349 binding sites between the nuclei varied by approximately eight-fold, with Bmax values ranging from 51.1 to 437.9 fmol/mg of tissue. The overall binding affinity was very high, yet the Kd

Discussion

The findings of this study demonstrate a high density of binding sites for the GABAB receptor antagonist [3H]CGP 62349 in almost all thalamic nuclei of the monkey brain. This is consistent with the results of Bowery et al.6 and Chu et al.10 on GABAB receptor site distribution in the rat thalamus detected with [3H]GABA as a ligand. Allowing for differences in the binding and measuring techniques in the two groups of studies, it appears that the overall number of GABAB binding sites for the

Conclusions

The findings of this study suggest that, in the monkey, the density of GABAB receptor sites in both the thalamus and basal ganglia is several-fold higher than in the rat. In the thalamus, only a portion of GABAB receptors is located presynaptically on NRT efferents, whereas the rest may be associated with several other GABAergic and non-GABAergic systems.

Acknowledgements

This study was made possible by R01 NS30983 to KKI and Medical Research Council for NGB. The authors thank Prof. V. Crunelli for thoughtful critique and helpful comments.

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