Aging alters in a region-specific manner serotonin transporter sites and 5-HT_1A receptor-G protein interactions in hamster brain

Key proteins regulating serotonergic activity, specifically the serotonin transporter and 5-HT_1A receptor, were examined in the midbrain raphe nuclei of young (3-4 months) and old (17-19 months) hamsters (N=7-10/group). An age-related decrease in the maximal density of serotonin transporter sites labelled with [³H]paroxetine (fmol/mg protein, Old: 396±13; Young: 487±27) was observed in the dorsal raphe nucleus (DRN) but not the median raphe nucleus (MRN), without affecting the affinity of [³H]paroxetine. In the DRN and MRN, the stimulation of [³⁵S]GTPγS binding by the 5-HT_1A receptor agonist 8-OH-DPAT, or the number of 5-HT_1A receptor sites labeled with [³H]MPPF, was not different in old versus young animals. Thus in the DRN, aging decreased serotonin transporter sites without changing 5-HT_1A receptor activation of G proteins or 5-HT_1A receptor density. In the CA₁ region of hippocampus, 8-OH-DPAT-stimulated [³⁵S]GTPγS binding was increased in the older animals (% above basal, Old: 141±21; Young: 81±17) without changing specific [³H]MPPF binding sites, suggesting that the capacity of 5-HT_1A receptors to activate G proteins is enhanced. Aging also appears to enhance this capacity in the dentate gyrus, because this region exhibited a constant level of 8-OH-DPAT-stimulated [³⁵S]GTPγS binding in spite of an age-related decrease in the number of [³H]MPPF binding sites (fmol/mg protein, Old: 203±21; Young: 429±51).