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  • 1
    ISSN: 1432-2072
    Keywords: Ageing ; 5-Hydroxytryptamine ; 5-HT agonist induced behaviours ; DOI ; 8-OH-DPAT ; [3H] Ketanserin binding
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Mature (3–4 months) and aged (18–19 months) Sprague-Dawley (SD) rats were treated with 5-HT receptor agonists and drug-induced behaviours monitored. The 5-HT2/1C agonist, 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI), induced wet dog shakes and back muscle contractions which were significantly increased in aged, compared to mature, rats, suggesting an age-related enhancement of 5-HT2 receptor function. In contrast, the selective 5-HT1A agonist 8-hydroxy-2-(di-n-propylamino) tetralin (8-OH-DPAT) induced forepaw treading, flat body posture, hypothermia and hyperactivity which were not significantly different in aged compared to mature rats. Levels of 5-HT and 5-hydroxyindoleacetic acid (5-HIAA) in the hippocampus and frontal cortex were measured using high performance liquid chromatography with electrochemical detection. There 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-related 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 [3H] 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 competition curve to DOI and reduced the proportion of high affinity agonist 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.
    Type of Medium: Electronic Resource
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