IN-VIVO EEDQ DOSE-DEPENDENTLY INACTIVATES RAT-BRAIN 5-HT RECEPTORS BUT NOT 5-HT UPTAKE SITES

THE present study investigates the inactivation and recovery of brain serotonin (5-HT) recognition sites by EEDQ (N-ethoxycarbonyl-2-ethoxy- 1,2,-dihydroquinoline), Adult male Sprague-Dawley rats were given a si ngle s.c. injection of vehicle (1:1 EtOH/H2O) or EEDQ (1-20 mg kg(-1)) and sacrificed at 4 h and 7 days (10 mg kg(-1) dose) postinjection. E EDQ dose-dependently reduced the Bmax of 5-HT1A (H-3-DPAT), 5-HT1B (I- 125-CYP), 5-HT2 H-3-ketanserin) and 5-HT2/1C (I-125-DOI) receptors in cortical homogenates. In contrast, EEDQ was without effect on the 5-HT transporter recognition site H-3-paroxetine). No significant changes in affinity were observed for 5-HT1B, 5-HT2 or 5-HT2/1C, receptors. Th e rank order of sensitivity to EEDQ inactivation was: 5-HT1A > 5-HT1B, > 5-HT2 approximate to 5-HT2/1C >>> 5-HT uptake sites. This study dem onstrates: (1) differential EEDQ inactivation and recovery of 5-HT rec eptors and (2) lack of EEDQ inactivation of the 5-HT transporter.