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.