EFFECTS OF A COLD ENVIRONMENT OR AGE ON METHAMPHETAMINE-INDUCED DOPAMINE RELEASE IN THE CAUDATE PUTAMEN OF FEMALE RATS
EFFECTS OF A COLD ENVIRONMENT OR AGE ON METHAMPHETAMINE-INDUCED DOPAMINE RELEASE IN THE CAUDATE PUTAMEN OF FEMALE RATS
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DOI：
10.1016/0091-3057(93)90284-z
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发表时间：
1993-01-01
影响因子：
3.6
通讯作者：
HOLSON, RR
中科院分区：
文献类型：
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作者：
BOWYER, JF;GOUGH, B;HOLSON, RR
采用微透析和高效液相色谱-电化学检测法（HPLC-ED）测定了6个月或12个月龄雌性大鼠尾壳核（CPU）中多巴胺（DA）及其代谢产物以及5-羟色胺（5-HT）和5-羟吲哚乙酸（5-HIAA）的细胞外水平，以及连续四次注射甲基苯丙胺（METH）后（间隔2小时）。在23 ℃的环境温度（ET）下，对6个月大的大鼠给予4 x 5 mg/kg METH，细胞外DA峰值水平（50 - 150 pg/10穆尔），而二羟基苯乙酸（DOPAC）在第一次剂量的METH后稳定下降，直到达到对照的50（550 - 700 pg/10穆尔）水平。在METH给药期间5-HT水平的增加会导致DA增加，而5-HIAA减少，DOPAC减少。在METH后3天，这些大鼠的总CPU DA和5-HT含量约为对照组的65%。在给药期间将ET降低至4 ℃，使4 x 5 mg/kg METH给药期间达到的峰值和平均DA水平降低至23 ℃ ET时观察到的水平的约50%。将剂量增加到4 x 10 mg/kg METH（4 ℃ ET）将峰值和平均CPU DA水平增加到23 ℃ ET下4 x 5 mg/kg METH期间观察到的200%。然而，在METH后3天，在4 ℃ ET下用METH给药的任何大鼠的总CPU DA含量均未观察到显著降低。在接受4 x 5 mg/kg METH（23摄氏度ET）给药的12月龄大鼠中，细胞外DA的峰值和平均水平仅为6月龄大鼠的30 - 60%。然而，老年大鼠的CPU DA含量显着降低3（30%控制）和14（60%控制）天后METH。总之，METH毒性可能不能仅通过METH给药期间获得的DA细胞外水平来预测;年龄和ET也极大地影响METH神经毒性。
Extracellular levels of dopamine (DA) and metabolites as well as serotonin [5-hydroxytryptamine (5-HT)] and 5-hydroxyindoleacetic acid (5-HIAA) were determined in the caudate putamen (CPU) of either 6- or 12-month-old female rats using microdialysis and high-performance liquid chromatography with electrochemical detection (HPLC-ED) before, during, and after four consecutive injections (given at 2-h intervals) of methamphetamine (METH). In 6-month-old rats administered 4 x 5 mg/kg METH at an environmental temperature (ET) of 23-degrees-C, peak extracellular DA levels (between 50 and 150 pg/10 mul) were attained 30-45 min after each dose of METH while dihydroxyphenylacetic acid (DOPAC) decreased steadily after the first doses of METH until it reached a plateau at 50% of control (550-700 pg/10 mul) levels. Increases in 5-HT levels during METH administrations paralleled DA increases while 5-HIAA decreases paralleled DOPAC decreases. The total CPU DA and 5-HT content of these rats was about 65% of control at 3 days post-METH. Reducing the ET to 4-degrees-C during dosing decreased the peak and average DA levels attained during the 4 x 5 mg/kg METH administration to about 50% of that observed at a 23-degrees-C ET. Increasing the dose to 4 x 10 mg/kg METH (4-degrees-C ET) increased peak and average CPU DA levels to 200% that observed during 4 x 5 mg/kg METH at a 23-degrees-C ET. However, no significant decreases in total CPU DA content of any rats dosed with METH at a 4-degrees-C ET were observed 3 days post-METH. In 12-month-old rats dosed with 4 x 5 mg/kg METH (23-degrees-C ET), the peak and average extracellular DA levels were only 30-60% that of 6-month-old rats. However, the CPU DA content of older rats was significantly decreased both 3 (30% control) and 14 (60% control) days post-METH. In summary, METH toxicity may not be predicted solely by the extracellular levels of DA attained during METH administration; age and ET also greatly influence METH neurotoxicity.