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.
Vinod
K Y
KY
Department of Neurochemistry, National Institute of Mental Health and Neurosciences, Bangalore, India.
Subhash
M N
MN
Srinivas
B N
BN
D017371:8-Hydroxy-2-(di-n-propylamino)tetralin / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000494:pharmacology; D000818:Animals; D001667:Binding, Competitive / Q000187:drug effects; D001921:Brain / Q000187:drug effects* / Q000378:metabolism*; D008297:Male; D011804:Quinolines / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011985:Receptors, Serotonin / Q000187:drug effects* / Q000378:metabolism*; D044263:Receptors, Serotonin, 5-HT1; D012702:Serotonin Antagonists / Q000494:pharmacology*; D017366:Serotonin Receptor Agonists / Q000378:metabolism / Q000494:pharmacology
D011804:Quinolines; D011985:Receptors, Serotonin; D044263:Receptors, Serotonin, 5-HT1; D012702:Serotonin Antagonists; D017366:Serotonin Receptor Agonists; C000470:EEDQ; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin