Corticosteroid receptor plasticity and recovery of a deficient hippocampus-associated behavior after unilateral (dorsal) hippocampectomy

Abstract

Unilateral ablation of the right dorsal hippocampus (HCX) produced changes in maximal corticosteroid binding capacity (B max) in the contralateral hippocampal lobe of the rat with time. The mechanism by which this time course of changes was produced seemed to involve the pituitary-adrenal system, since a certain difference in corticosteroid receptor binding pattern was noted between chronic adrenalectomized (ADX) rats and rats which remained intact during postlesion survival. In the presence of endogenous adrenal hormones the HCX-induced changes in corticosteroid receptor binding relative to that observed in rats with the overlying neocortex ablated (control) were the following: (1) a 26% decrease at 5 days after HCX; (2) an increase the following 3 weeks with a maximum of 46% at 20 days postsurgery; and (3) recovery towards control values after longer survival times. After discrimination of corticosteroid binding into two corticosterone (CORT) binding receptor populations, e.g. glucocorticoid receptors (GR) and mineralocorticoid-like or CORT receptors (CR), the lesion-induced effect was more pronounced in GR than in CR. A 72% increase over controls was measured at 20 days postsurgery. In the absence of the adrenals, however, the B max of corticosteroid binding was not decreased at 5 days after HCX. The relative increase in B max reached a maximum of 39% over control levels at 30 days postsurgery and recovery towards control values after longer survival did not occur. The increase in corticosteroid receptor capacity after HCX, therefore, is transient in the presence of adrenocortical secretion and permanent in its absence. An attempt was made to relate the changes in corticosteroid receptor capacity to deficits in reversal learning behavior, since it is known that this type of behavior is associated with hippocampus function. Reversal learning behavior in a T-shaped maze was disturbed the first 2 weeks after HCX, but restored the following week. ADX seemed to facilitate recovery of the lesion-induced deficit. Bilateral removal of the hippocampus led to a more permanent deficiency in reversal learning behavior. It is concluded that: (1) unilateral HCX induces a period of considerable plasticity in corticosteroid receptors in particular of the GR type; (2) this receptor plasticity coincides with the recovery of a lesion-induced deficit in hippocampus-associated behavior; and (3) a role of adrenal hormones in regulation of neuronal and corticosteroid receptor plasticity cannot be excluded.