ACUTE RISE IN CORTICOSTERONE FACILITATES 5-HT1A RECEPTOR-MEDIATED BEHAVIORAL-RESPONSES

Corticosterone influences 5-HT1A receptor-mediated responses in the ra t hippocampus in vitro: activation of the high affinity mineralocortic oid receptor suppresses 5-HT1A receptor-mediated hyperpolarization, wh ile subsequent activation of lower affinity glucocorticoid receptors e nhances the effect of 5-HT. We have tested whether a similar effect of corticosterone exists in vivo. In intact rats, a systemic injection o f the specific 5-HT1A receptor agonist, 8-OH-DPAT (8-hydroxy-2-(di-n-p ropylamino)tetralin) led to increased locomotion and to a less persist ent search strategy in the free swim trial of the Morris water maze te st. Adrenalectomized rats with a corticosterone-pellet implanted as re placement received an injection of vehicle (predominant mineralocortic oid receptor occupation) or a high dose of corticosterone (both cortic osteroid receptor types occupied) 1 h before injection of 8-OH-DPAT. T he effect on search strategy, but not on locomotor activity, was less in animals with low corticosterone levels. The results suggest that hi ppocampal 5-HT1A receptor-mediated responses in vivo are attenuated du ring predominant activation of the mineralocorticoid receptor and incr eased after additional transient activation of the glucocorticoid rece ptor. (C) 1998 Elsevier Science B.V. All rights reserved.