Journal of Neuroscience, Vol 9, 3237-3242, Copyright © 1989 by Society for Neuroscience
Apparent age-related resistance of type II hippocampal corticosteroid receptors to down-regulation during chronic escape training
JC Eldridge, A Brodish, TE Kute and PW Landfield
Department of Physiology and Pharmacology, Bowman Gray School of Medicine of Wake Forest University, Winston-Salem, North Carolina 27103.
Corticosteroids appear to modulate neuronal loss in the hippocampus during
aging. However, there is a seeming paradox in the literature in that
age-related neuronal loss develops more prominently during the later phases
of the lifespan, whereas brain corticosterone receptors have been reported
to decline with aging, an effect that might be anticipated to reduce the
impact of corticosteroids on cell loss. In order to study the regulatory
sensitivity of hippocampal corticosteroid receptors (HCSR) during aging,
which could play a role in this apparent paradox, rats of 3 ages (4, 12,
and 18 months old at the start of training) were given 6 months of chronic
escape training using a mild footshock in a 2-way shuttle-escape task (4
hr/d, 5 d/week). Animals were killed either 1 d or 3 weeks following the 6
month training paradigm. Nontrained home cage controls also were maintained
in parallel with each age group. Although previous studies have measured
receptors in rats adrenalectomized 12 hr or more prior to death, rats
intact at death were used in the present studies to avoid possible
confounding effects from age differences in receptor up-regulation or
response to surgery. Receptor capacity was analyzed with a saturation assay
able to measure available type II HCSR in intact rats. Results showed that,
in intact young-mature rats (10 months old at death), type II HCSR were
down-regulated at 1 d, but not at 3 weeks, after the end of the 6 months of
training. However, significant decreases in HCSR were not observed in late
mid-aged (18-month-old) or aged (24-month- old) rats at the 1 d point,
indicating apparent resistance to down- regulatory stimuli.(ABSTRACT
TRUNCATED AT 250 WORDS)