AGE-DEPENDENT LOSS OF CORTICOSTERONE MODULATION OF CENTRAL SEROTONIN 5-HT1A RECEPTOR-BINDING SITES

A loss of endocrine and neurotransmitter system interactions, includin g corticosterone regulation of 5-HT1A receptors, may underlie the age- related deficits in the hypothalamic-pituitary-adrenal (HPA) axis incl uding adapting to stress. In this study, female Fischer 344 rats, (age s 3, 13, and 18 months), were bilaterally adrenalectomized and supplem ented for 3 weeks with placebo or corticosterone (200 mg or 600 mg) co ntaining 21 day sustained-release pellets implanted subcutaneously (LC , MC, or HC, respectively). Scatchard analysis using the 5-HT1A recept or agonist [H-3]8-hydroxy-2-(di-N-propylamino) tetralin (8-OH-DPAT) de monstrated a significant decrease in hippocampal receptor density in 3 month and 13 month MC groups (-35.2 and -32.1%, respectively) as comp ared to age-matched LC groups; a significant decline in 5-HT1A recepto r 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 hor mone treatments (LC or HC) failed to alter hippocampal 5-HT1A binding site density in the 18 month groups. Cortical 5-HT1A receptor densitie s were altered in a similar age-dependent manner. In contrast, the den sity of hypothalamic 5-HT1A receptors in the 18 month LC group was sig nificantly increased above that in the 3 month LC group. An additional indicator of the hippocampal response to corticosterone, the distribu tion of glial fibrillary acidic protein (GFAP), revealed an age-relate d decline in responsiveness to hormone treatment in the oldest group. The present study has identified an age-associated deficit in the regu lation of hippocampal 5-HT1A receptors by corticosterone which may und erlie the diminished capacity of the aging HPA axis to cope with stres s. J. Neurosci. Res. 53:86-98, 1998. (C) 1998 Wiley-Liss, Inc.