| Summary: | 碩士 === 國立陽明大學 === 生理學研究所 === 94 === 英文摘要
Amphetamine (AMPH) is a highly addictive drug of abuse which is neurotoxic to dopamine terminal. Amphetamine changes the expressions of the dopamine transporter (DAT) and vesicular monoamine transporter 2 (VMAT 2) in rat brain and causes some unusual behaviors. However, the effective ways to cure problems of drug abuse are still open to study. Previously we have found that intermittent hypoxia reduces the basal level of dopamine in the diencephalons. Some studies indicated that administration of estrogen significantly attenuates the degree of striatal dopamine depletion to neurotoxins (MPTP, 6-OHDA and methamphetamine) which target the nigrostriatal dopaminergic system. The present study was to explore the effects of estradiol on the levels of striatal dopamine in ovariectomized (Ovx) rats treated with or without amphetamine following intermittent hypoxia. Female rats were Ovx for two weeks before administration of amphetamine (5 mg/kg, i.p.) with or without estradiol (25 µg/kg, s.c.) once daily for 7 days in combination with or without intermittent hypoxia for 7 days. The striatal and mPFC tissues were collected, homogenized with dopamine mobile phase and then centrifuged at 4℃, 8000 �e g for 10 min. The concentrations of dopamine in the supernatants were detected by HPLC. The protein expressions of DAT, VMAT-2 and tyrosine hydroxylase (TH) were analyzed by western blotting. The results indicated that in normoxia, AMPH could attenuate dopamine level significantly in both mPFC and striatum ( P<0.01). Comparing to control groups, administration of either estradiol or estradiol plus AMPH increased dopamine level ( P<0.01). Both mPFC and striatal dopamine levels following intermittent hypoxia were similar to normoxia levels. The protein expression of both mPFC and striatal DAT were significant greater ( P<0.01) in rats treated with amphetamine or intermittent hypoxia plus estradiol than in amphetamine-treated or intermittent hypoxic animals. After intermittent hypoxia, the DAT expressions in both mPFC and striatum were decreased comparing to normoxia group. These results suggest that the dopamine levels in both mPFC and striatum can be enhanced by estradiol via an increase of DAT expression following administration of either amphetamine or intermittent hypoxia.
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