AGE-RELATED BEHAVIORAL, NEUROCHEMICAL AND RADIOLIGAND BINDING CHANGESIN THE CENTRAL 5-HT SYSTEM OF SPRAGUE-DAWLEY RATS

Mature(3-4 months) and aged (18-19 months) Sprague-Dawley (SD) rats we re treated with 5-HT receptor agonists and drug-induced behaviours mon itored. The 5-HT2/(1C) agonist, 1-(2,5-dimethoxy-4-iodophenyl)-2-amino propane (DOI), induced wet dog shakes and back muscle contractions whi ch were significantly increased in aged, compared to mature, rats, sug gesting an age-related enhancement of 5-HT2 receptor function. In cont rast, the selective 5-HT1A agonist 8-hydroxy-2-(di-n-propylamino) tetr alin (8-OH-DPAT) induced forepaw treading, flat body posture, hypother mia and hyperactivity which were not significantly different in aged c ompared to mature rats. Levels of 5-HT and 5-hydroxyindoleacetic acid (5-HIAA) in the hippocampus and frontal cortex were measured using hig h performance liquid chromatography with electrochemical detection. Th ere were no age-related changes in hippocampal 5-HT or 5-HIAA. However both 5-HT and 5-HIAA were increased in the frontal cortex of aged SD rats. 8-OH-DPAT reduced 5-HIAA in both regions examined in mature rats , an effect which was attenuated in the aged rats, suggesting an age-r elated reduction in presynaptic 5-HT1A receptor function. DOI did not induce any changes in 5-HT or 5-HIAA in either of the regions examined . Radioligand binding studies with [H-3] ketanserin showed there to be no significant age-related changes in cortical 5-HT2 receptor density or affinity. In the samples taken from mature rats GTP shifted the co mpetition curve to DOI and reduced the proportion of high affinity ago nist binding sites; this effect was not observed in the aged samples, suggesting that there may be age-related changes in G-protein-mediated receptor-effector coupling mechanisms.