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.
Maines
L W
LW
Department of Pharmacology, The Pennsylvania State University College of Medicine, Hershey 17033-0850, USA.
Keck
B J
BJ
Dugar
A
A
Lakoski
J M
JM
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