Ascorbic Acid Reduces Accumulation of [ 3 H]Spiperone in Mouse Striatum in Vivo

Abstract

[³H]Spiperone was administered (20 μCi/kg, 0.0003 mg/kg, sc) to mice. In agreement with other published reports, 2 hr later the accumulation of tritium was three to four times greater in the corpus striatum than in the cerebellum. Ascorbic acid (100, 1000, 2000 mg/kg, ip, 30 min) reduced the 2-hr accumulation in the corpus striatum 16, 42, and 63%, respectively, with only the highest dose producing any significant (18%) reduction in the cerebellum. The effect was still evident in striatum 18 hr after a single dose of 1000 mg/kg. Striatal minces taken from mice treated 1 or 2 hr earlier with ascorbic acid (2000 mg/kg, ip) showed no reduction in [³H]spiperone binding. However, preincubation of striatal minces for 2 hr with ascorbic acid (10⁻³ M) produced an 82% reduction in specific binding while not having any effect on nonspecific binding. While it cannot be certain that the reduction of striatal [³H]spiperone concentrations after ascorbic acid in vivo was not a result of some nonspecific alteration in the pharmacokinetics of [³H]spiperone, the in vitro observation strongly suggests that it resulted from an alteration of binding characteristics at the receptor level.