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-HT1A receptors was studied in Sprague Dawley rats. A single dose of EEDQ (4 mg/kg body wt., i.p.) significantly inactivated 5-HT1A receptors, as measured by [3H]8-hydroxy-2-[di-n-propylamino]-tetralin ([3H]8-OH-DPAT), in cortex (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 observed in both regions. A dose dependent protection of cortical 5-HT1A receptors from EEDQ inactivation with pre-treatment of different doses of 8-OH-DPAT (4-20 mg/kg) was observed, along with recovery of affinity of [3H]8-OH-DPAT 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 receptors, a significant protection of these receptors was observed with 10 and 20 mg/kg of 8-OH-DPAT. Displacement studies revealed that EEDQ has more affinity 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 receptors from inactivation by a single dose of EEDQ (4 mg/kg) was observed more in cortex compared to hippocampus over a period from 1 day to 14 days. The 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.