[3H]-8-OH-DPAT binding in the rat brain raphe area:: involvement of 5-HT1A and non-5-HT1A receptors

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 the 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): 6.04+/-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]-citalopram (a selective 5-HT uptake inhibitor) were determined. There was a significant correlation between pK(i) values at 5-HT uptake sites and at non-5HT(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 for the non-5-HT1A site than S(-)8-OH-DPAT and was considered as an outlier in the correlation. It is suggested that [H-3]-8-OH-DPAT labels other, as yet unknown binding sites in the raphe.