FURTHER CHARACTERIZATION OF [H-3] 8-HYDROXY-2(DI-N-PROPYLAMINO)TETRALIN BINDING-SITES IN HUMAN BRAIN POSTMORTEM

The saturation parameters and the pharmacological characteristics of t he binding of the serotonin 1A (5-HT1A) receptor agonist [H-3]8-hydrox y-2-(di-N-propylamino)tetralin ([H-3]8-OH-DPAT), as well as the effect s of nucleotides and divalent cations (Mg2+, Mn2+) on it, were compare d in some human postmortem brain regions: the main cortical areas, hip pocampus and striatum. [H-3]8-OH-DPAT labelled a single population of recognition sites with the highest maximal capacity (B-max) in the hip pocampus and the lowest affinity in the striatum. Among the Various co rtical areas, the frontal cortex exhibited the highest B-max. The phar macological profile of the [H-3]8-OH-DPAT binding sites was consistent with the labelling of the 5-HT1A receptor in the hippocampus and cort ex, whereas the striatal site shared strong similarity to the presynap tic serotonin transporter. Modulation of [H-3]8-OH-DPAT binding by div alent cations and nucleotides was detectable and stable in autopsy bra ins. In particular, nucleotide effects were area-dependent: guanosine thiotriphosphate (GTP gamma S) reduced [H-3]8-OH-DPAT binding to the s ame extent in the hippocampus and frontal cortex, while having no effe ct in the striatum. Divalent cation effects depended also upon the bra in area: in the striatum, they inhibited [H-3]8-OH-DPAT binding, while stimulating it in the hippocampus and, with less extent, in the front al cortex. In summary, these findings suggest that the [H-3]8-OH-DPAT binding and its modulatory parameters in human brain tissues seem to s how similarities but also some differences with respect to those deter mined in the rat brain. Furthermore, postmortem stability of GTP and d ivalent cation sensitive 5-HT1A receptors underlines the need for furt her studies on the regulatory and functional properties of this recept or in the human brain. Copyright (C) 1996 Elsevier Science Ltd