SELECTIVE DECLINE OF 5-HT1A RECEPTOR-BINDING SITES IN RAT CORTEX, HIPPOCAMPUS AND CHOLINERGIC BASAL FOREBRAIN NUCLEI DURING AGING

The effect of aging on 5-HT1A receptor binding in several forebrain ar eas associated with the basal forebrain cholinergic system was investi gated in rats of 3-, 24- and 30-months-old by receptor autoradiography and biochemical binding assay using [H-3]8-OH-DPAT as a ligand. Autor adiographic measurements demonstrated a marked region-specific decline of ligand binding in: (i) regions of the basal forebrain cholinergic cell groups, i.e. the medial septum, diagonal band nuclei and magnocel lular nucleus basalis, (ii) the frontal and parietal neocortex and (ii i) the dentate gyrus of the hippocampus. No change or- only a slight d ecrease of the 5-HT1A receptor density was found in other areas invest igated: the CA1 and CA3 sectors of hippocampus, the cingular and perir hinal cerebral cortex and the lateral septum. The autoradiographic fin dings were substantiated by the biochemical binding assay, which revea led a comparable loss of 5-HT1A receptor in the hippocampus and neocor tex at the age of 30 months. The results clearly show that with increa sing age the decrement of 5-HT1A receptor binding in the rat forebrain is remarkably region-selective and particularly affects the cholinerg ic cell groups that innervate cortex and hippocampus. This phenomenon appears to be especially significant in relation to the neuronal subst rates underlying the age-related alterations of mood and cognition. (C ) 1997 Elsevier Science B.V.