Age-related assessment of central 5-HT1A receptors following irreversible inactivation by N-ethoxycarbonyl-2-ethoxy-1,2-dihydroquinoline (EEDQ).
Age-dependent differences in the ability of N-ethoxycarbonyl-2-ethoxy-1,2-dihydroquinoline (EEDQ) to irreversibly inactivate 5-HT1A receptors were investigated in female Fischer 344 rats (ages 3 and 22 months). In the hippocampus, frontal cortex and amygdala, EEDQ reduced 5-HT1A receptor density (33-70%) and drug affinity (2.3-6.2 fold) as determined by Scatchard analyses using [3H]8-hydroxy-2-(di-N-propylamino)tetralin. In the frontal cortex, the reduction in Bmax values was significantly greater in 3 months vs. 22 months groups. These region-specific and age-dependent alterations in 5-HT1A receptors may be of pathophysiological significance in age-related cognitive decline and Alzheimer's disease.
Keck
J
J
Department of Pharmacology, Milton S. Hershey Medical Center, Pennsylvania State University College of Medicine, Hershey 17033, USA.
Lakoski
J M
JM
D000375:Aging / Q000378:metabolism*; D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D005069:Evaluation Studies as Topic; D005260:Female; D009498:Neurotoxins / Q000633:toxicity*; D011804:Quinolines / Q000633:toxicity*; D051381:Rats; D011916:Rats, Inbred F344; D012702:Serotonin Antagonists / Q000633:toxicity*
D009498:Neurotoxins; D011804:Quinolines; D012702:Serotonin Antagonists; C000470:EEDQ