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
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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