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Corticosterone regulation of serotonin transporter and 5‐HT 1A receptor expression in the aging brain
Author(s) -
Maines Lynn W.,
Keck B. Jane,
Smith Jane E.,
Lakoski Joan M.
Publication year - 1999
Publication title -
synapse
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.809
H-Index - 106
eISSN - 1098-2396
pISSN - 0887-4476
DOI - 10.1002/(sici)1098-2396(199904)32:1<58::aid-syn8>3.0.co;2-r
Subject(s) - endocrinology , medicine , serotonergic , corticosterone , agonist , hippocampal formation , serotonin , serotonin transporter , hippocampus , 5 ht1a receptor , receptor , chemistry , 5 ht receptor , hormone
Abstract Hypercortisolemia is often observed in patients suffering from major depression. As the serotonergic (5‐hydroxytryptamine; 5‐HT) system plays a major role in the etiology of depression, a loss of endocrine and neurotransmitter system interactions, including corticosterone regulation of 5‐HT transporter (5‐HTT) and 5‐HT receptor expression, may underlie age‐related deficits in the regulation of the hypothalamic‐pituitary‐adrenal (HPA) axis and correlate with an increased incidence of depression with advancing age. In this study, female Fischer 344 rats, ages 3, 13, and 18 months, were bilaterally adrenalectomized and supplemented for 3 weeks with corticosterone (0, 200, or 600 mg; LC, MC, or HC, respectively) containing 21 day sustained‐release pellets implanted subcutaneously. Quantitative autoradiography of hippocampal and cortical regions using [ 3 H]citalopram revealed a significant decrease in hippocampal 5‐HTT binding in the 3‐month HC treatment group compared to age‐matched MC and LC groups; this loss was not present in the 13‐ or 18‐month groups. Similarly, quantitative autoradiography using the radiolabeled 5‐HT 1A receptor agonist 8‐hydroxy‐2‐(di‐ N ‐propylamino) tetralin demonstrated a significant decline in receptor density in 3‐ and 13‐month MC and HC groups as compared to age‐matched LC groups in the hippocampus. These hormone treatments (MC or HC), however, failed to alter hippocampal 5‐HT 1A binding site density in the 18‐month groups as compared to the age‐matched LC group. The 5‐HT 2A receptor was also evaluated using [ 3 H]ketanserin and showed no age‐ or corticosterone‐related changes in the cortex. Overall, an age‐associated deficit in the regulation of the hippocampal serotonergic system by varied corticosterone treatment was revealed in the present study, which may underlie the increased incidence of depression and hypercortisolemia found with advancing age. Synapse 32:58–66, 1999. © 1999 Wiley‐Liss, Inc.