Autoradiography of CCK receptors in the rat brain using [(3)H]Boc[Nle(28)(31)]CCK(27)-(33) and [(125)I]bolton-hunter CCK(8). Functional significance of subregional distributions.
[(3)H]Boc[Nle(28,31)]CCK(27)-(33) ([(3)H]BDNL-CCK(7)) is a new ligand for cholecystokinin (CCK) receptors, endowed with a high specific activity (100 Ci/mmol). Binding sites for this ligand were visualized in the rat brain by autoradiography [(3)H]BDNL-CCK(7) binds specifically to an apparent single class of CCK receptors on rat striatum sections with a K(d) of 1.76 nM and a B(max) of 57 fmol/mg protein. Unsulfated CCK(8) was two times less potent than sulfated CCK(8) to displace binding of [(3)H]BDNL-CCK(7). Binding sites for [(3)H]BDNL-CCK(7) were present in many brain regions, the highest concentrations occurring in cortex, olfactory bulbs, nucleus accumbens, and medium to high concentrations in striatum, hippocampus, and several nuclei of thalamus, hypothalamus and amygdala. In the same experimental conditions, the binding sites for [(125)I]BH-CCK(8) showed similar specificity and localization. We thus used both ligands to investigate the subregional distributions of CCK receptors in nucleus accumbens and hippocampus, where a highly organized topography of action of CCK has been reported. In nucleus accumbens, the CCK binding sites were concentrated in the anterior portion of the nucleus, whereas very low densities were observed within medial posterior nucleus accumbens, where injection of CCK has been shown to potentiate dopamine-induced hyperlocomotion. p]In hippocampus, CCK receptors were concentrated in the polymorphic zone of the hilus of the dentate gyrus and in stratum lacunosum moleculare of Ammon's horn. Very few receptors were observed in other regions of hippocampus, including stratum pyramidale and stratum moleculare. This is in contrast with the presence of numerous CCK terminals and the potent effect of CCK in these areas. The distributions of CCK receptors reported here in both nucleus accumbens and hippocampus were discussed in correlation with the distribution of CCK neurons and terminals, the related anatomical pathways, and the pharmacological profiles of the effects of CCK in these regions.
Pélaprat
D
D
Département de Chimie Organique, U266 INSERM, UA498 CNRS, UER des Sciences Pharmaceutiques et Biologiques, 4 avenue de l'Observatoire, 75006 Paris, France.
Broer
Y
Y
Studler
J M
JM
Peschanski
M
M
Tassin
J P
JP
Glowinski
J
J
Rostène
W
W
Roques
B P
BP