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Age-related behavioural, neurochemical and radioligand binding changes in the central 5-HT system of Sprague-Dawley rats

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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.

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Authors and Affiliations

  1. Department of Physiology and Pharmacology, Queen's Medical Centre, NG7 2UH, Nottingham, UK

    Lindsay Robson, D. A. Kendall & C. A. Marsden

  2. Department of Neuropharmacology, UCB Pharma, Chemin du Foriest, B1420, Braine 1'Alleud, Belgium

    A. J. Gower

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  1. Lindsay Robson
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  3. D. A. Kendall
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  4. C. A. Marsden
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Robson, L., Gower, A.J., Kendall, D.A. et al. Age-related behavioural, neurochemical and radioligand binding changes in the central 5-HT system of Sprague-Dawley rats. Psychopharmacology 113, 274–281 (1993). https://doi.org/10.1007/BF02245710

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