Methamphetamine treatment affects blood and liver S-adenosylmethionine (SAM) in mice. Correlation with dopamine depletion in the striatum.
Methamphetamine (METH) is a major drug of abuse which causes neurotoxicity by depleting dopamine, its metabolites, high-affinity dopamine uptake sites and tyrosine hydroxylase activity in the striatum. Dopamine depletion and reduced dopamine transit are associated with depression. S-Adenosylmethionine (SAM) is the chief methyl donor used in dopamine and other neurotransmitter metabolism in mammals. Low SAM is associated with depression and other psychological and neurological disorders in humans. SAM is used to treat depression and some other neurological and psychiatric disorders. The present study was designed to determine if single or multiple doses of METH induce alterations in blood or liver SAM in mice and if these correlate with dopamine levels in the striatum. Adult male C57 mice were injected intraperitoneally with either single (1 x 40 mg/kg) or multiple (4 x 10 mg/kg) doses of METH. Animals were sacrificed at various intervals. A single injection of METH resulted in slightly higher blood SAM levels at 4 hr. Multiple doses of METH resulted in decreased hepatic and blood SAM levels at 72 hr. Blood SAM returned to control levels by 1 wk. Published work shows that dopamine levels increase hours after a single injection of METH, whereas dopamine decreases days after multiple injections of METH. These present data clearly demonstrate that METH dosing leads to significant alterations in liver and blood SAM and that these changes in SAM levels correlate with changes in striatal dopamine levels.
Division of Molecular Epidemiology, National Center for Toxicological Research/FDA Jefferson, Arkansas 72079-9502, USA.
C A
CA
Cooney
C K
CK
Wise
L A
LA
Poirier
S F
SF
Ali
D000818:Animals; D000697:Central Nervous System Stimulants / Q000494:pharmacology*; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism*; D004298:Dopamine / Q000172:deficiency*; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D008694:Methamphetamine / Q000494:pharmacology*; D051379:Mice; D008810:Mice, Inbred C57BL; D012436:S-Adenosylmethionine / Q000097:blood / Q000378:metabolism*
D000697:Central Nervous System Stimulants; D008694:Methamphetamine; D012436:S-Adenosylmethionine; D004298:Dopamine