Differential protection and recovery of 5-HT1A receptors from N-ethoxycarbonyl-2-ethoxy-1, 2-dihydroquinoline (EEDQ) inactivation in regions of rat brain

The effect of N-ethoxycarbonyl-2-ethoxy-1,2-dihydroquinoline (EEDQ) on 5-HT 1A receptors was studied in Sprague Dawley rats. A single dose of EEDQ (4 m g/kg body wt., i.p.) significantly inactivated 5-HT1A receptors, as measure d by [H-3]8-hydroxy-2-[di-n-propylamino]tetralin ([H-3]8-OH-DPAT), in corte x (64%, p < 0.0001) and hippocampus (48%, p < 0.0001). A significant (p < 0 .01) increase in the affinity of 5-HT1A receptors for radioligand was obser ved in both regions. A dose dependent protection of cortical 5-HT1A recepto rs from EEDQ inactivation with pre-treatment of different doses of 8-OH-DPA T (4-20 mg/kg) was observed, along with recovery of affinity of [H-3]8-OH-D PAT for 5-HT1A receptors in both regions. Although, a dose of 4 mg/kg of 8- OH-DPAT failed to attenuate the effect of EEDQ on hippocampal 5-HT1A recept ors, a significant protection of these receptors was observed with 10 and 2 0 mg/kg of 8-OH-DPAT. Displacement studies revealed that EEDQ has more affi nity for cortical (Ki = 101.3 +/- 11.8 nM) than hippocampal (Ki = 133.5 +/- 25.8 nM) 5-HT1A receptors. A time dependent natural recovery of 5-HT1A rec eptors from inactivation by a single dose of EEDQ (4 mg/kg) was observed mo re in cortex compared to hippocampus over a period from I day to 14 days. T he results of this study suggest that 8-OH-DPAT inhibited EEDQ inactivation of cortical and hippocampal 5-HT1A receptors in a concentration dependent manner. The synthesis and turnover of 5-HT1A receptors differ in cortex and hippocampus, as evident by earlier recovery in the cortex.