Effects of Intermittent Hypoxia on Brain Dopamine Levels in Rats Treated with Amphetamine

• Main Authors: Shu-Yun Cheng, 鄭淑云
• Other Authors: Paulus S. Wang
• Format: Others
• Language: zh-TW
• Published: 2004
• Online Access: http://ndltd.ncl.edu.tw/handle/79503235034296101063

碩士 === 國立陽明大學 === 生理學研究所 === 92 === 　Amphetamine is a highly addictive drug of abuse that is neurotoxic to dopamine terminals. Amphetamine changes the expression of the dopamine transporter (DAT) and vesicular monoamine transporter 2 (VMAT 2) in rat brain and then causes the unusual behavior. However, the effective ways to cure problems of drug abuse are still open to study. We have previously found that intermittent hypoxia reduces the basal level of dopamine in the diencephalon and increases plasma prolactin concentration. In the present study, the effect of intermittent hypoxia on the dopamine release in rats treated with or without amphetamine was investigated. Rats were divided into four groups including normoxia, hypoxia, amphetamine treatment, and amphetamine plus hypoxia groups. The normoxia and hypoxia groups were injected with normal saline as vehicle control. The rats in hypoxia group were housed in a box of 12% O2 plus 88% N2, 8 h per day for 7 days. These rats were injected with or without amphetamine daily (5 mg/kg) for 7 days. The rats treated with amphetamine plus hypoxia were injected with amphetamine daily for 7 days and then housed in a hypoxic box for 8 h daily for 7 days. After pretreatment, the cerebrospinal fluid was collected by microdialysis every 20 min and the dopamine levels in the dialysates were detected by HPLC. Rat plasma was collected every 40 min and the prolactin concentration was measured by radioimmunoassay. We found that intermittent hypoxia reduced the concentration of dopamine in the media prefrontal cortex and increased that in the striatum. Dopamine levels were increased despite rats treated with intermittent hypoxia or with amphetamine plus intermittent hypoxia. Furthermore, intermittent hypoxia failed to lower the responses to Ang II in the media prefrontal cortex and striatum but enhanced the responses. The plasma prolactin concentration increased in the hypoxic groups. Otherwise, amphetamine plus intermittent hypoxia would increase tyrosine hydroxylase expression in the prefrontal cortex. At the same time, intermittent hypoxia or amphetamine treatment would decrease the expression of VMAT-2 in the rat brain. However, whether rats treated with amphetamine or intermittent hypoxia, the expression of dopamine transporter did not changed. These data suggest that intermittent hypoxia would alter the dopamine release and change the protein expression in different nucleus in the brain. Intermittent hypoxia did play an important role in regulating dopamine metabolism in rat brain.