Chronic methamphetamine exposure decreases high affinity uptake function in norepinephrine afferents in the cerebellar cortex: An electrophysiological and electrochemical study

Yun Wang, Jenny Chou, C. H. Jeng, M. Morales, J. Y. Wang

研究成果: 雜誌貢獻文章同行評審

10 引文 斯高帕斯(Scopus)

摘要

It has been reported that chronic methamphetamine (MA) treatment decreases monoamine release in different brain regions. However, the clearance of norepinephrine (NE) after chronic MA intake is not clear. In the present study, we administered MA to Sprague-Dawley rats for 1 month. The animals were later anesthetized with urethane for electrophysiological recording. Previous studies have indicated that γ-aminobutyric acid (GABA)- induced electrophysiological responses are enhanced by norepinephrine (NE) acting via postsynaptic β-adrenergic receptors. We found that local application of the NE high affinity uptake inhibitor desmethylimipramine (DMI) significantly potentiated GABA-induced electrophysiological depressions in cerebellar Purkinje neurons in control rats. In contrast, DMI did not augment GABA responses in rats chronically treated with MA for 1 month, or in rats withdrawn from MA for 7-14 days after a 1-month MA treatment. To further examine if DMI-induced GABA modulation is altered by post- or pre-synaptic mechanisms in chronic MA-treated rats, we examined the electrophysiological interaction of GABA and isoproterenol (ISO), a postsynaptic β-adrenergic receptor agonist, in Purkinje neurons. We found that GABA-induced inhibition is potentiated by local application of ISO in both control and chronic MA rats, suggesting that the reduction in DMI/GABA interactions is probably not mediated through post-synaptic noradrenergic mechanisms. Presynaptic NE clearance was further examined using in vivo chronoamperometric methods. Extracellular NE levels in the cerebellar cortex were measured using Nafion- coated carbon fiber sensors. We found that local application of DMI inhibited NE clearance in control rats, but not in chronic MA animals, suggesting that presynaptic NE clearance is reduced after chronic MA treatment. In addition, NE levels in cerebellar tissue were measured using HPLC-ECD. The NE concentration was significantly decreased in chronic MA rats. Taken together, our data suggest that regulation of uptake by DMI at central noradrenergic nerve terminals is abnormal after chronic MA exposure. (C) 2000 Elsevier Science Ltd.
原文英語
頁(從 - 到)2112-2123
頁數12
期刊Neuropharmacology
39
發行號11
DOIs
出版狀態已發佈 - 10月 2000
對外發佈

ASJC Scopus subject areas

  • 細胞與分子神經科學
  • 藥物發現
  • 藥理

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