Ascorbic acid reduces accumulation of [3H]spiperone in mouse striatum in vivo.
[3H]Spiperone was administered (20 microCi/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.
D000818:Animals; D001058:Apomorphine / Q000494:pharmacology; D001205:Ascorbic Acid / Q000494:pharmacology*; D002531:Cerebellum / Q000032:analysis; D003342:Corpus Striatum / Q000032:analysis / Q000187:drug effects*; D003864:Depression, Chemical; D018492:Dopamine Antagonists; D004357:Drug Synergism; D006220:Haloperidol / Q000494:pharmacology; D051379:Mice; D011954:Receptors, Dopamine / Q000187:drug effects* / Q000378:metabolism; D013134:Spiperone / Q000378:metabolism*
D018492:Dopamine Antagonists; D011954:Receptors, Dopamine; D013134:Spiperone; D006220:Haloperidol; D001058:Apomorphine; D001205:Ascorbic Acid