Effects of methamphetamine on central monoaminergic systems in normal and ascorbic acid-deficient guinea pigs.
Repeated injections (s.c.) of methamphetamine (METH) were administered to normal and ascorbic acid-deficient (scorbutic) guinea pigs to assess a potential role for ascorbic acid in the METH-induced effects in central monoaminergic systems. The ascorbic acid-deficient condition differentially influenced the METH-induced responses of dopaminergic and serotonergic variables in the striatum: drug-induced changes in dopaminergic variables were identical in normal and scorbutic animals; METH-induced decreases in serotonergic variables [tryptophan hydroxylase activity, serotonin (5-HT) and 5-hydroxyindoleacetic acid concentrations], however, were prevented in scorbutic animals. The scorbutic condition did not alter significantly the distribution of METH in the brain, nor were striatal concentrations of dopamine (DA) or 5-HT affected. In vitro, ascorbic acid increased significantly DA-mediated [3H]5-HT release from striatal slices, thus suggesting a potential role for ascorbate in DA-mediated actions of METH on serotonergic systems. Although supplemental ascorbate failed to restore the METH-induced serotonergic effects in scorbutic guinea pigs, these data suggest that, in a normal animal, the effects of multiple injections of METH, on serotonergic systems, involve ascorbic acid.
Matsuda
L A
LA
Department of Pharmacology and Toxicology, University of Utah, Salt Lake City 84112.
Schmidt
C J
CJ
Gibb
J W
JW
Hanson
G R
GR
D000661:Amphetamine / Q000032:analysis; D000818:Animals; D001206:Ascorbic Acid Deficiency / Q000378:metabolism*; D001921:Brain / Q000187:drug effects*; D003342:Corpus Striatum / Q000032:analysis; D005260:Female; D006168:Guinea Pigs; D006897:Hydroxyindoleacetic Acid / Q000032:analysis; D008694:Methamphetamine / Q000032:analysis / Q000494:pharmacology*; D011954:Receptors, Dopamine / Q000187:drug effects*; D011985:Receptors, Serotonin / Q000187:drug effects*; D012701:Serotonin / Q000032:analysis; D014365:Tryptophan Hydroxylase / Q000032:analysis
D011954:Receptors, Dopamine; D011985:Receptors, Serotonin; D012701:Serotonin; D008694:Methamphetamine; D006897:Hydroxyindoleacetic Acid; D000661:Amphetamine; D014365:Tryptophan Hydroxylase