Methamphetamine treatment rapidly inhibits serotonin, but not glutamate, transporters in rat brain.
Previous studies have demonstrated that multiple methamphetamine (METH) administrations rapidly and reversibly decrease dopamine transporter activity assessed in striatal synaptosomes. A role for reactive oxygen species was suggested by findings that: (1) METH treatment increases the formation of oxygen radicals in vivo; and (2) oxygen radicals, generated by the enzyme xanthine oxidase, attenuate dopamine uptake in vitro. To test the selectivity of transporter responses, the present study examined effects of METH and xanthine oxidase on [3H]serotonin ([3H]5HT) and [3H]glutamate transport into striatal synaptosomes. Multiple doses of METH, or incubation with xanthine oxidase, rapidly attenuated [3H]5HT transport; an effect attributable to a decrease in Vmax. The METH-induced decrease in transport activity completely recovered by 24 h, but was decreased again 1 week later. In contrast, [3H]glutamate transport was essentially unchanged after METH treatment or incubation with xanthine oxidase. These findings indicate that: (1) METH causes a rapid and reversible decrease in 5HT transporter activity; and (2) glutamate transporters are less susceptible than 5HT transporters to effects of reactive species or METH treatment.
Kokoshka
J M
JM
Department of Pharmacology and Toxicology, University of Utah, 112 Skaggs Hall, Salt Lake City, UT 84112, USA.
Metzger
R R
RR
Wilkins
D G
DG
Gibb
J W
JW
Hanson
G R
GR
Fleckenstein
A E
AE
D018528:ATP-Binding Cassette Transporters / Q000378:metabolism*; D027322:Amino Acid Transport System X-AG; D000818:Animals; D002352:Carrier Proteins / Q000037:antagonists & inhibitors*; D003342:Corpus Striatum / Q000187:drug effects* / Q000378:metabolism*; D018698:Glutamic Acid / Q000493:pharmacokinetics; D008297:Male; D008562:Membrane Glycoproteins / Q000037:antagonists & inhibitors*; D026901:Membrane Transport Proteins; D008694:Methamphetamine / Q000494:pharmacology*; D009419:Nerve Tissue Proteins; D051381:Rats; D017207:Rats, Sprague-Dawley; D012701:Serotonin / Q000493:pharmacokinetics; D050486:Serotonin Plasma Membrane Transport Proteins; D013574:Synaptosomes / Q000187:drug effects / Q000378:metabolism; D013997:Time Factors; D014969:Xanthine Oxidase / Q000494:pharmacology
D018528:ATP-Binding Cassette Transporters; D027322:Amino Acid Transport System X-AG; D002352:Carrier Proteins; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; D050486:Serotonin Plasma Membrane Transport Proteins; C493232:Slc6a4 protein, rat; D012701:Serotonin; D018698:Glutamic Acid; D008694:Methamphetamine; D014969:Xanthine Oxidase