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 oxyge n species was suggested by findings that: (1) METH treatment increases the formation of oxygen radicals in vivo; and (2) oxygen radicals, ge nerated by the enzyme xanthine oxidase, attenuate dopamine uptake in v itro. To test the selectivity of transporter responses, the present st udy examined effects of METH and xanthine oxidase on [H-3]serotonin ([ H-3]5HT) and [H-3]glutamate transport into striatal synaptosomes. Mult iple doses of METH, or incubation with xanthine oxidase, rapidly atten uated [H-3]5HT transport; an effect attributable to a decrease in V-ma x. The METH-induced decrease in transport activity completely recovere d by 24 h, but was decreased again 1 week later. In contrast, [H-3]glu tamate transport was essentially unchanged after METH treatment or inc ubation with xanthine oxidase. These findings indicate that: (1) METH causes a rapid and reversible decrease in 5HT transporter activity; an d (2) glutamate transporters are less susceptible than 5HT transporter s to effects of reactive species or METH treatment. (C) 1998 Elsevier Science B.V. All rights reserved.