Regional heterogeneity of serotonin(1A) receptor inactivation and turnover in the aging female rat brain following EEDQ.
The turnover of serotonin(1A) (5-HT(1A)) receptors was investigated in several brain regions of young adult (3 months) and old (22 months) female Fischer 344 rats following irreversible inactivation by N-ethoxycarbonyl-2-ethoxy-1,2-dihydroquinoline (EEDQ). Equilibrium binding analyses for the 5-HT(1A) receptor binding site incorporated [(3)H]8-hydroxy-2-(di-N-propylamino)tetralin ([(3)H]8-OH-DPAT) and were conducted in the frontal cortex, amygdala and hippocampus at 1, 2, 7 and 14 days after treatment with EEDQ (6.0 mg/kg, s.c.) or vehicle. The pattern of 5-HT(1A) receptor recovery following EEDQ treatment was found to be age- and region-dependent. For example, in the hippocampus, receptor recovery occurred at a faster rate in the old rats compared to young adult rats. While a significant decrease in affinity for the 5-HT(1A) receptor was found in the frontal cortex and amygdala in young adult and old rats following EEDQ, B(MAX) values for [(3)H]8-OH-DPAT binding in these brain regions were unaltered by EEDQ across age groups. In the frontal cortex and amygdala, significant age-dependent decreases in affinity for the 5-HT(1A) receptor were revealed at day 1 following EEDQ administration. The significance of the present findings is discussed in terms of aging and a regionally-defined sensitivity of 5-HT(1A) receptors to the irreversible inactivator EEDQ.
Keck
B J
BJ
Department of Pharmacology and Anesthesia, The Milton S. Hershey Medical Center, The Pennsylvania State University College of Medicine, 500 University Drive, Hershey, PA 17033-0850, USA. bjk11@psu.edu
Lakoski
J M
JM
D017371:8-Hydroxy-2-(di-n-propylamino)tetralin / Q000378:metabolism / Q000494:pharmacology; D000375:Aging / Q000378:metabolism*; D000679:Amygdala / Q000187:drug effects / Q000378:metabolism; D000818:Animals; D001923:Brain Chemistry / Q000187:drug effects*; D002245:Carbon Dioxide / Q000378:metabolism; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism; D005260:Female; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism; D007700:Kinetics; D011804:Quinolines / Q000494:pharmacology*; D011869:Radioligand Assay; D051381:Rats; D011916:Rats, Inbred F344; 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; D002245:Carbon Dioxide; C000470:EEDQ; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin