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Selective decline of 5-HT1A receptor binding sites in rat cortex, hippocampus and cholinergic basal forebrain nuclei during aging Nyakas, C; Oosterink, BJ; Felszeghy, K; deJong, GI; Korf, J; Luiten, PGM; Keijser, Jan N. Link to publication in University of Groningen/UMCG research database Citation for published version (APA): Nyakas, C., Oosterink, BJ., Felszeghy, K., deJong, GI., Korf, J., Luiten, PGM., & Keijser, J. N. (1997). Selective decline of 5-HT1A receptor binding sites in rat cortex, hippocampus and cholinergic basal forebrain nuclei during aging. Journal of Chemical Neuroanatomy, 13(1), 53-61. https://doi.org/10.1016/S0891-0618(97)00025-2 Copyright Other than for strictly personal use, it is not permitted to download or to forward/distribute the text or part of it without the consent of the author(s) and/or copyright holder(s), unless the work is under an open content license (like Creative Commons).Take-down policy If you believe that this document breaches copyright please contact us providing details, and we will remove access to the work immediately and investigate your claim.Downloaded from the University of Groningen/UMCG research database (Pure): http://www.rug.nl/research/portal. For technical reasons the number of authors shown on this cover page is limited to 10 maximum. AbstractThe effect of aging on 5-HT 1A receptor binding in several forebrain areas associated with the basal forebrain cholinergic system was investigated in rats of 3-, 24-and 30-months-old by receptor autoradiography and biochemical binding assay using [ 3 H]8-OH-DPAT as a ligand. Autoradiographic 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 magnocellular nucleus basalis, (ii) the frontal and parietal neocortex and (iii) the dentate gyrus of the hippocampus. No change or only a slight decrease of the 5-HT 1A receptor density was found in other areas investigated: the CA1 and CA3 sectors of hippocampus, the cingular and perirhinal cerebral cortex and the lateral septum. The autoradiographic findings were substantiated by the biochemical binding assay, which revealed a comparable loss of 5-HT 1A receptor in the hippocampus and neocortex at the age of 30 months. The results clearly show that with increasing age the decrement of 5-HT 1A receptor binding in the rat forebrain is remarkably region-selective and particularly affects the cholinergic cell groups that innervate cortex and hippocampus. This phenomenon appears to be especially significant in relation to the neuronal substrates underlying the age-related alterations of mood and cognition. © 1997 Elsevier Science B.V.

Recent evidence indicates that serotonin (5-HT)1A receptor agonists may abrogate excitotoxic brain damage. We investigated whether a single i.p. injection of the 5-HT1A receptor agonist 8-hydroxy-2-(di-n-propylamino) tetralin (8-OH-DPAT), at a dose of 2.5 mg/kg, protects cholinergic neurons of the rat magnocellular nucleus basalis (MBN) against NMDA excitotoxicity when administered at post-injury intervals ranging from 6 to 96 h. Drug effects on passive avoidance learning and on the density of cortical cholinergic innervation, a measure of neuronal survival in the damaged MBN, were analyzed. Our results demonstrate that 8-OH-DPAT, when administered up to 24 h post-lesion, significantly attenuates both behavioral and neuroanatomical consequences of NMDA excitotoxicity on cholinergic MBN neurons; and support the hypothesis that 5-HT1A receptor agonists may interfere with delayed neuronal death in vivo that is of significance in the pharmacological treatment of neurological disorders associated with excitotoxic neuronal damage.

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