Age-dependent loss of corticosterone modulation of central serotonin 5-HT1A receptor binding sites.
A loss of endocrine and neurotransmitter system interactions, including corticosterone regulation of 5-HT1A receptors, may underlie the age-related deficits in the hypothalamic-pituitary-adrenal (HPA) axis including adapting to stress. In this study, female Fischer 344 rats, (ages 3, 13, and 18 months), were bilaterally adrenalectomized and supplemented for 3 weeks with placebo or corticosterone (200 mg or 600 mg) containing 21 day sustained-release pellets implanted subcutaneously (LC, MC, or HC, respectively). Scatchard analysis using the 5-HT1A receptor agonist [3H]8-hydroxy-2-(di-N-propylamino) tetralin (8-OH-DPAT) demonstrated a significant decrease in hippocampal receptor density in 3 month and 13 month MC groups (-35.2 and -32.1%, respectively) as compared to age-matched LC groups; a significant decline in 5-HT1A receptor density in 3 month and 13 month HC groups was found compared to age-matched MC groups (-16.7 and -22.0%, respectively). However, these hormone treatments (LC or HC) failed to alter hippocampal 5-HT1A binding site density in the 18 month groups. Cortical 5-HT1A receptor densities were altered in a similar age-dependent manner. In contrast, the density of hypothalamic 5-HT1A receptors in the 18 month LC group was significantly increased above that in the 3 month LC group. An additional indicator of the hippocampal response to corticosterone, the distribution of glial fibrillary acidic protein (GFAP), revealed an age-related decline in responsiveness to hormone treatment in the oldest group. The present study has identified an age-associated deficit in the regulation of hippocampal 5-HT1A receptors by corticosterone which may underly the diminished capacity of the aging HPA axis to cope with stress.
Department of Pharmacology, The Pennsylvania State University College of Medicine, Hershey 17033-0850, USA.
L W
LW
Maines
B J
BJ
Keck
A
A
Dugar
J M
JM
Lakoski
D000315:Adrenalectomy; D000375:Aging / Q000502:physiology*; D000818:Animals; D001665:Binding Sites; D001923:Brain Chemistry / Q000502:physiology*; D002540:Cerebral Cortex / Q000254:growth & development / Q000502:physiology; D003345:Corticosterone / Q000097:blood / Q000494:pharmacology / Q000502:physiology*; D005260:Female; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D005911:Gliosis / Q000473:pathology; D006624:Hippocampus / Q000254:growth & development / Q000502:physiology; D007150:Immunohistochemistry; D011869:Radioligand Assay; D051381:Rats; D011916:Rats, Inbred F344; D011985:Receptors, Serotonin / Q000502:physiology*
D005904:Glial Fibrillary Acidic Protein; D011985:Receptors, Serotonin; D003345:Corticosterone