The effect of corticosterone on reactivity to spatial novelty is mediated by central mineralocorticosteroid receptors.
Corticosterone, secreted by the adrenal glands, binds to central mineralocorticoid receptors with high affinity and to glucocorticoid receptors with a tenfold lower affinity. In previous studies we have shown that the selective activation of either mineralocorticoid receptors or glucocorticoid receptors exerts distinctly different behavioural effects. In this study we examined in particular the mineralocorticoid receptor-mediated effect of corticosterone on the control of the behavioural response of male Wistar rats to spatial novelty. This analysis was based on our observation that in adrenal-intact rats the presence of an object in the centre of an open field alters the time spent and distance walked in the centre compared to the peripheral area, i.e. the pattern of reactive locomotor activity is changed. Using this paradigm we found that 1 day after removal of the adrenals the rats increased their behavioural reactivity towards the object. Treatment of adrenalectomized rats with a low dose of corticosterone (50 micrograms/kg s.c.) 1 h prior to testing restored the behavioural reactivity to the level of sham-operated, intact rats. Surprisingly, a high dose of corticosterone (1000 micrograms/kg s.c.) also increased the rat's reactivity towards the object. The same high dose of corticosterone given to adrenal-intact rats also increased behavioural reactivity. Pretreatment of these rats with an intracerebroventricular injection of the selective mineralocorticoid receptor antagonist RU28318 (100 ng/microliters) prevented the corticosterone-induced increase in behavioural reactivity, while the blockade of glucocorticoid receptors with the antagonist RU38486 (100 ng/microliters) was not effective. Administration of the mineralocorticoid receptor antagonist without corticosterone to adrenal-intact rats also increased behavioural reactivity, but this increase did not reach statistical significance.(ABSTRACT TRUNCATED AT 250 WORDS)
Oitzl
M S
MS
Leiden/Amsterdam Centre for Drug Research, University of Leiden, The Netherlands.
Fluttert
M
M
de Kloet
E R
ER
D000315:Adrenalectomy; D000324:Adrenocorticotropic Hormone / Q000097:blood; D000818:Animals; D003345:Corticosterone / Q000008:administration & dosage / Q000097:blood / Q000494:pharmacology*; D005106:Exploratory Behavior / Q000187:drug effects* / Q000502:physiology; D008124:Locomotion / Q000187:drug effects; D008297:Male; D015735:Mifepristone / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D011965:Receptors, Glucocorticoid / Q000187:drug effects; D018161:Receptors, Mineralocorticoid / Q000187:drug effects / Q000502:physiology*; D013037:Spatial Behavior / Q000187:drug effects* / Q000502:physiology; D013148:Spironolactone / Q000031:analogs & derivatives / Q000494:pharmacology
D011965:Receptors, Glucocorticoid; D018161:Receptors, Mineralocorticoid; D013148:Spironolactone; D015735:Mifepristone; C041006:RU 28318; D000324:Adrenocorticotropic Hormone; D003345:Corticosterone