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

• Published in: Neurochemical research 2001-02, Vol.26 (2), p.113-120
• Main Authors: VINOD, K. Y, SUBHASH, M. N, SRINIVAS, B. N
• Format: Article
• Language: English
• Subjects: 8-Hydroxy-2-(di-n-propylamino)tetralin - antagonists & inhibitors; 8-Hydroxy-2-(di-n-propylamino)tetralin - metabolism; 8-Hydroxy-2-(di-n-propylamino)tetralin - pharmacology; Animals; Binding, Competitive - drug effects; Biological and medical sciences; Brain - drug effects; Brain - metabolism; Central nervous system; Central neurotransmission. Neuromudulation. Pathways and receptors; Fundamental and applied biological sciences. Psychology; Male; Quinolines - pharmacology; Rats; Rats, Sprague-Dawley; Receptors, Serotonin - drug effects; Receptors, Serotonin - metabolism; Receptors, Serotonin, 5-HT1; Serotonin Antagonists - pharmacology; Serotonin Receptor Agonists - metabolism; Serotonin Receptor Agonists - pharmacology; Vertebrates: nervous system and sense organs
• ISSN: 0364-3190; 1573-6903
• DOI: 10.1023/A:1011038510723

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.