The brain was quickly exposed, hemisected tests and ANOVA (StatView; Abacus Concepts, Berkeley, CA). al., 1990;Moyer et al., 1996; Thompson et al., 1996b). Also, both the AHP and accommodation are greater in CA1 neurons from aging rabbits (Moyer GNE-207 et al., 1992) and rats (Landfield and GNE-207 Pitler, 1984; Potier et al., 1992) as compared with that from young animals. The current study was designed to determine (1) the effects, (2) the effective concentrations of bath application of metrifonate on CA1 neurons from hippocampal slices of young and aging rabbits, (3) whether chronic metrifonate treatment in aging rabbits alters basal CA1 excitability Small (<3 month) and aging (>36 month) female New Zealand albino rabbits (have not been explored in either age group; and (4) previous work has demonstrated that metrifonate unequally increased the ACh levels in the hippocampus of young and aging subjects (Scali et al., 1997), thus, bath application of metrifonate access to food and water. The animal care was provided and managed by the animal care staff of Northwestern University or college after the guidelines established by the university or college and the Rabbit polyclonal to UBE2V2 United GNE-207 States Department of Agriculture. Hippocampal slices were made using procedures previously explained (Moyer et al., 1996; Thompson et al., 1996b). The rabbits were anesthetized with halothane in a fume hood and killed by decapitation. The brain was quickly uncovered, hemisected assessments and ANOVA (StatView; Abacus Concepts, Berkeley, CA). Significant main effects were evaluated using Scheffestests. All data are reported as the imply SEM. Using comparable procedures to those previously published (Kronforst-Collins et al., 1997b), aging (>40 month) rabbits received 15 oral doses (5 d of treatment followed by 2 d of no treatment repeated for three weeks) of either 12 mg/kg metrifonate dissolved in a 100 mm sodium citrate vehicle (= 4; imply age, 41.31 0.06 months) or vehicle alone (= 3; imply age, 41.00 0.13 months). Previously, 12 mg/kg metrifonate was found to produce optimum facilitation of trace eyeblink conditioning in aging rabbits (Kronforst-Collins et al., 1997a,b). Blood samples were taken from all subjects 1 d before the start of treatment and 2 hr before killing. Twenty-four hours after the last treatment, hippocampal slices were prepared, and CA1 neurons were recorded from as described above. AHP, accommodation, and input resistance were measured sequentially as described above in aCSF, aCSF with 50 m metrifonate, and aCSF with 50 m GNE-207 metrifonate plus 1 matropine perfusates with 10 min intervals between changes in the perfusate. The experimenter was blind to the identity of the chronic treatment during the daily administration, blood sampling, electrophysiological recordings, and data reduction until the end of the experiment. The level of ChE inhibition was measured using procedures described by Kronforst-Collins et al. (1997a,b). The subjects were given fentanyl citrate and droperidol anesthesia (0.5 ml/kg, i.m.) before blood sampling. Each blood sample was collected in two 1.5 ml aliquot tubes each containing 50 l of heparin. The samples were centrifuged at 1000 tests. Metrifonate was a gift from Bayer Corporation (West Haven, CT). All other drugs used were purchased from Sigma (St. Louis, MO). Eserine and atropine stocks were made and used in near darkness. Stock solution of metrifonate (pH 4.0) was prepared weekly and refrigerated (3C) along with the other stock solutions. RESULTS Metrifonate decreased the AHP amplitude and?area Metrifonate significantly decreased the AHP peak amplitude and integrated area in CA1 neurons from both young and aging subjects (Figs. ?(Figs.11< 0.006;< 0.046, respectively). No depression was observed in the neurons GNE-207 from aging rabbits at this concentration (> 0.309; > 0.178, respectively). Instead, a significant reduction of the AHP amplitude was observed with 50 m metrifonate in the neurons from aging rabbits (< 0.009); the AHP area was not significantly reduced, although a trend toward the reduction was observed (< 0.074). Decrements in both AHP peak amplitude and integrated area for the neurons from aging rabbits were observed with 100 m metrifonate (< 0.002; < 0.001, respectively). The neurons from young rabbits depolarized to levels at which.