Region-specific serotonin1A receptor turnover following irreversible blockade with EEDQ

The neurotoxicant N-ethoxycarbonyl-2-ethoxy-1,2-dihydroquinoline (EEDQ) irreversibly inactivates serotonin1A (5-HT1A) receptors and is a useful tool to investigate the kinetics of receptor recovery following administration of the drug. Recovery characteristics were determined for 5-HT1A receptors located in the frontal cortex and hippocampus of male Sprague-Dawley rats treated with EEDQ (6.0 mgth kg-1, s.c.) or vehicle. Saturation binding assays using [3H]8-OH-DPAT were conducted, using frontal cortex and hippocampal membrane homogenates, at several time points following EEDQ treatment (1, 2, and 8 days post-injection). Scatchard analyses revealed region-specific differences in the recovery of these receptors. 5-HT1A receptors in the hippocampus degraded more quickly but recovered faster than those in the frontal cortex; receptor half-life was also shorter in the hippocampus than in frontal cortex. These regional variations are discussed in terms of differential receptor synthesis. The pathophysiological relevance of these findings to aging and disorders involving 5-HT1A receptor dysfunction, including depression and anxiety, is discussed.