Mb. Assie et W. Koek, [H-3]-8-OH-DPAT binding in the rat brain raphe area: involvement of 5-HT1Aand non-5-HT1A receptors, BR J PHARM, 130(6), 2000, pp. 1348-1352
The 5-HT1A agonist 8-OH-DPAT has been shown to have additional 5-HT uptake
inhibiting properties. The present work was undertaken to examine further t
he binding of [H-3]-8-OH-DPAT in the raphe area of the rat brain, a region
rich in 5-HT1A receptors and 5-HT uptake sites.
2 5-HT inhibited [H-3]-8-OH-DPAT binding in a biphasic manner (pK(i1): 8.82
+/-0.01, pK(i2): 6.07+/-0.05, n=4) with the low affinity site representing
36+/-4% of the total population. A biphasic inhibition curve was found also
with the 5-HT1A antagonist, WAY 100635 (pK(i1): 8.65+/-0.17, pK(i2): 4.26/-0.38, n=3). In the presence of 1 mu M WAY 100635 to mask 5-HT1A receptors
, 5-HT inhibited [H-3]-8-OH-DPAT binding in a monophasic manner (pK(i): 6.0
4+/-0.07, n=3).
3 The affinities of various compounds for sites labelled by [H-3]-8-OH-DPAT
in the presence of 1 mu M WAY 100635 and for sites labelled by [H-3]-cital
opram (a selective 5-HT uptake inhibitor) were determined. There was a sign
ificant correlation between pK(i) values at 5-HT uptake sites and at non-5H
T(1A) sites labelled by [H-3]-8-OH-DPAT (r=0.80, P<0.001, n=17), suggesting
these latter sites to be 5-HT uptake sites.
4 Whereas the affinities of R(+) and S(-) enantiomers of 8-OH-DPAT for the
5-HT uptake site are similar, R(+)8-OH-DPAT has 10 times higher affinity fo
r the non-5-HT1A site than S(-)8-OH-DPAT and was considered as an outlier i
n the correlation. It is suggested that [H-3]-8-OH-DPAT labels other, as ye
t unknown binding sites in the raphe.