[3H]-8-OH-DPAT binding in the rat brain raphe area: Involvement of 5-HT(1A) and non-5-HT(1A) receptors

Abstract

1. The 5-HT(1A) 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 [3H]-8-OH-DPAT in the raphe area of the rat brain, a region rich in 5-HT(1A) receptors and 5-HT uptake sites. 2. 5-HT inhibited [3H]-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-HT(1A) antagonist, WAY 100635 (pK(i1): 8.65 ± 0.17, pK(i2): 4.26 ± 0.38, n = 3). In the presence of 1 μM WAY 100635 to mask 5-HT(1A) receptors, 5-HT inhibited [3H]-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 [3H]-8-OH-DPAT in the presence of 1 μM WAY 100635 and for sites labelled by [3H]-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 [3H]-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 RC(+) 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-HT(1A) site than S(-)8-OH-DPAT and was considered as an outlier in the correlation. It is suggested that [3H]-8-OH-DPAT labels other, as yet unknown binding sites in the raphe.