3H]8-OH-DPAT labels the 5-hydroxytryptamine uptake recognition site and the 5-HT1A binding site in the rat striatum

The binding of 3H]8-hydroxy-2-(di-N-propylamino)-tetralin ( 3H]8-OH-DPAT) to rat hippocampal and striatal membranes has been compared. In the hippocampus, low concentrations of 3H]8-OH-DPAT bound to a single, high affinity site which was sensitive to inhibition by spiperone, buspirone and ergotamine but not by mianserin, quipazine or (-)-propranolol. This is consistent with a selective labeling of the 5-HT1A receptor. In the striatum, 3H]8-OH-DPAT bound to two sites with high and low affinity (KD's 1.18 and 109 nM). The high affinity component was blocked by low concentrations of buspirone, spiperone and ergotamine. The low affinity component was blocked only by high concentrations of buspirone and spiperone, and was not displaced by ergotamine at concentrations up to 1 microM. The ergotamine-resistant component of striatal 3H]8-OH-DPAT binding was blocked by low concentrations of the 5-HT uptake inhibitors fluvoxamine and paroxetine, and by relatively low concentrations of 5-HT itself. Thus 3H]8-OH-DPAT labels the 5-HT transporter in the rat striatum. Unlike 3H]imipramine binding, the binding of 3H]8-OH-DPAT to the 5-HT transporter was independent of external sodium ions. It is therefore suggested that 8-OH-DPAT acts as substrate for the 5-HT transporter and labels the 5-HT recognition site of the transporter complex.