Attenuation and recovery of evoked overflow of striatal serotonin in rats treated with neurotoxic doses of methamphetamine

被引:16
作者
Cass, WA [1 ]
机构
[1] Univ Kentucky, Chandler Med Ctr, Dept Anat & Neurobiol, Coll Med, Lexington, KY 40536 USA
关键词
methamphetamine; serotonin; striatum; microdialysis; neurotoxicity;
D O I
10.1046/j.1471-4159.2000.0741079.x
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Repeated administration of methamphetamine to animals can lead to long-lasting decreases in striatal monoamine content. In the present study, the effects of neurotoxic doses of methamphetamine on basal and evoked overflow of striatal serotonin and of its primary metabolite 5-hydroxyindoleacetic acid were examined in awake rats using in vivo microdialysis, Male Fischer-344 rats were administered methamphetamine (5 mg/kg, s.c.) or saline four times in I day at 2-h intervals. Microdialysis studies were carried out 1 week, 1 month, and 6 months later. At 1 week posttreatment there were significant decreases in potassium- and amphetamine-evoked overflow of serotonin in the striatum of the methamphetamine-treated animals. Basal extracellular levels of 5-hydroxyindoleacetic acid but not of serotonin were also decreased. Evoked overflow of serotonin recovered by 1 month, and extracellular levels of 5-hydroxyindoleacetic acid had recovered by 6 months. Tissue levels of serotonin and 5-hydroxyindoleacetic acid were decreased at 1 week posttreatment but back to control levels by 1 month after treatment. These results indicate that presynaptic serotonergic functioning is attenuated in the striatum of rats treated 1 week earlier with neurotoxic doses of methamphetamine, However, in the model used, the changes are transient, and recovery can occur within 1-6 months posttreatment.
引用
收藏
页码:1079 / 1085
页数:7
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