THE EFFECT OF CORTICOSTERONE ON REACTIVITY TO SPATIAL NOVELTY IS MEDIATED BY CENTRAL MINERALOCORTICOSTEROID RECEPTORS

Corticosterone, secreted by the adrenal glands, binds to central miner alocorticoid receptors with high affinity and to glucocorticoid recept ors with a tenfold lower affinity. In previous studies we have shown t hat the selective activation of either mineralocorticoid receptors or glucocorticoid receptors exerts distinctly different behavioural effec ts. In this study we examined in particular the mineralocorticoid rece ptor-mediated effect of corticosterone on the control of the behaviour al response of male Wistar rats to spatial novelty. This analysis was based on our observation that in adrenal-intact rats the presence of a n object in the centre of an open field alters the time spent and dist ance walked in the centre compared to the peripheral area, i.e. the pa ttern of reactive locomotor activity is changed. Using this paradigm w e found that 1 day after removal of the adrenals the rats increased th eir behavioural reactivity towards the object. Treatment of adrenalect omized rats with a low dose of corticosterone (50 mu g/kg s.c.) 1 h pr ior to testing restored the behavioural reactivity to the level of sha m-operated, intact rats. Surprisingly, a high dose of corticosterone ( 1000 mu g/kg s.c.) also increased the rat's reactivity towards the obj ect. The same high dose of corticosterone given to adrenal-intact rats also increased behavioural reactivity. Pretreatment of these rats wit h an intracerebroventricular injection of the selective mineralocortic oid receptor antagonist RU28318 (100 ng/mu l) prevented the corticoste rone-induced increase in behavioural reactivity, while the blockade of glucocorticoid receptors with the antagonist RU38486 (100 ng/mu l) wa s not effective. Administration of the mineralocorticoid receptor anta gonist without corticosterone to adrenal-intact rats also increased be havioural reactivity, but this increase did not reach statistical sign ificance. General locomotor activity was not affected by either treatm ent. In conclusion, we found a U-shaped relationship between the patte rn of behavioural reactivity in a novel environment and the circulatin g plasma corticosterone level, The response to spatial novelty appeare d to be sensitive with respect to the activation and blockade of centr al, presumably hippocampal mineralocorticoid receptors.