Activation of 5-HT1A but not 5-HT1B receptors attenuates an increase in extracellular dopamine derived from exogenously administered L-DOPA in the striatum with nigrostriatal denervation

被引:124
作者
Kannari, K
Yamato, H
Shen, H
Tomiyama, M
Suda, T
Matsunaga, M
机构
[1] Hirosaki Univ, Sch Med, Dept Med 3, Hirosaki, Aomori 0368216, Japan
[2] Hirosaki Univ, Sch Med, Dept Neurol, Hirosaki, Aomori 0368216, Japan
关键词
5-HT1A receptor; 5-HT1B receptor; L-DOPA; dopamine; 6-OHDA-lesioned rat; microdialysis;
D O I
10.1046/j.1471-4159.2001.00184.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
In order to determine whether L-DOPA-derived extracellular dopamine (DA) in the striatum with dopaminergic denervation is affected by activation of serotonin autoreceptors (5-HT1A and 5-HT1B receptors), we applied in vivo brain microdialysis technique to 6-hydroxydopamine-lesioned rats and examined the effects of the selective 5-HT1A receptor agonist 8-hydroxy2-(di-n-propylamino)tetralin (8-OH-DPAT) and the selective S-HT1B receptor agonist CGS-12066 A on L-DOPA-derived extracellular DA levels. Single L-DOPA injection (50 mg/kg i.p.) caused a rapid increase and a following decrease of extracellular DA, with a peak value at 100 min after L-DOPA injection. Pretreatment with both 0.3 mg/kg and 1 mg/kg 8-OH-DPAT (i.p.) significantly attenuated an increase in L-DOPA-derived extracellular DA and the times of peak DA levels were prolonged to 150 min and 225 min after L-DOPA injection, respectively. These 8-OH-DPAT-induced changes in L-DOPA-derived extracellular DA were antagonized by further pretreatment with WAY-100635, a selective 5-HT1A antagonist. In contrast, intrastriatal perfusion with the 5-HT1B agonist CGS-12066 A (10 nM and 100 nM) did not induce any changes in L-DOPA-derived extracellular DA. Thus, stimulation of 5-HT1A but not 5-HT1B receptors attenuated an increase in extracellular DA derived from exogenous L-DOPA. These results support the hypothesis that serotonergic neurons are primarily responsible for the storage and release of DA derived from exogenous L-DOPA in the absence of dopaminergic neurons.
引用
收藏
页码:1346 / 1353
页数:8
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