TIME-COURSE OF THE EFFECTS OF ADRENALECTOMY AND CORTICOSTERONE REPLACEMENT ON 5-HT1A RECEPTORS AND 5-HT UPTAKE SITES IN THE HIPPOCAMPUS ANDDORSAL RAPHE NUCLEUS OF THE RAT-BRAIN - AN AUTORADIOGRAPHIC ANALYSIS

Previous studies have shown that adrenalectomy (ADX) increases the bin ding of H-3-DPAT to 5-HT1A receptors in the hippocampus (HIP) and this effect is partially overcome by corticosterone (CORT) replacement. Th e present study investigated the time course of the effects of ADX wit h or without CORT replacement on serotonin (5-HT) pre- and postsynapti c systems in the HIP and dorsal raphe nucleus (DR) by quantitative aut oradiography. In the HIP, ADX for 7, 10 or 14 days caused a significan t increase in H-3-DPAT binding in the CA, region (pyramidal layer), CA (2,3) region (molecular and pyramidal layers) and in the dentate gyrus (molecular and granular layers) which returned to control levels when measurements were made 35 days post-ADX. A decrease in H-3-DPAT bindi ng was observed 14 days after ADX in the DR but not in the median raph e nucleus (MR). Although replacement with CORT did not lead to a rever sal in H-3-DPAT binding at early time points, binding was restored to control levels 7-28 days after CORT replacement in all regions of the HIP. In the DR, CORT did not cause a reversal in H-3-DPAT binding at a ny of the time points examined. In contrast to the effects seen on the 5-HT1A receptor subtype, no significant change was noted on the bindi ng of H-3-CN-IMI to uptake sites for 5-HT in the HIP or DR after ADX o r CORT replacement. The results of this study indicate that long-term alterations in the HPA axis lead to changes in the 5-HT1A receptor sys tem that are both region-specific and time-dependent.