Methamphetamine-induced modification of dopamine metabolism in cultured striatal astrocytes.
The role of striatal astrocytes in the metabolic processing (by deamination) of methamphetamine-released dopamine is not known. To investigate the relationship between methamphetamine and dopamine metabolism, we measured 6-hydroxydopamine, dopamine and, 3,4-dihydroxyphenylacetic acid (DOPAC) concentrations following methamphetamine treatment of cultured striatal astrocytes prepared from 1-2 day-old rats. Addition of low concentrations of dopamine (5 x 10(-5) to 5 x 10(-4) M) to cultured astrocytes increased DOPAC levels in a dose-dependent fashion while higher concentrations (5 x 10(-3) to 10(-2) M) inhibited its metabolism and induced formation of 6-hydroxydopamine. Under the same experimental conditions, 10(-4) M dopamine in combination with methamphetamine (10(-5) to 10(-3) M) inhibited DOPAC formation and increased dopamine levels in a dose-dependent fashion, but the formation of intracellular 6-hydroxydopamine was not evident. Deprenyl (10(-5) or 10(-4) M), an inhibitor of monoamine oxidase B, and pargyline (10(-5) or 10(-4) M), a non-selective monoamine oxidase inhibitor, completely inhibited DOPAC formation and increased dopamine levels, while clorgyline (10(-5) or 10(-4) M), an inhibitor of monoamine oxidase-A, only partially inhibited DOPAC formation (42 or 45% of control, respectively). These results support the hypothesis that methamphetamine inhibits monoamine oxidase and causes increases in dopamine levels in cultured striatal astrocytes.
Department of Pharmacology and Toxicology, Rutgers University, New Brunswick, New Jersey 08903, USA.
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T
Kita
M A
MA
Philbert
G C
GC
Wagner
J
J
Huang
H E
HE
Lowndes
D015102:3,4-Dihydroxyphenylacetic Acid / Q000378:metabolism; D000818:Animals; D000831:Animals, Newborn; D001253:Astrocytes / Q000187:drug effects* / Q000378:metabolism; D002478:Cells, Cultured; D003342:Corpus Striatum / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D004298:Dopamine / Q000378:metabolism*; D018765:Dopamine Uptake Inhibitors / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D008694:Methamphetamine / Q000494:pharmacology*; D008996:Monoamine Oxidase Inhibitors / Q000494:pharmacology; D016627:Oxidopamine / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley
D018765:Dopamine Uptake Inhibitors; D008996:Monoamine Oxidase Inhibitors; D015102:3,4-Dihydroxyphenylacetic Acid; D008694:Methamphetamine; D016627:Oxidopamine; D004298:Dopamine