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
Article first published online: 20 DEC 2001
Journal of Neurochemistry
Volume 76, Issue 5, pages 1346–1353, March 2001
How to Cite
Kannari, K., Yamato, H., Shen, H., Tomiyama, M., Suda, T. and Matsunaga, M. (2001), 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. Journal of Neurochemistry, 76: 1346–1353. doi: 10.1046/j.1471-4159.2001.00184.x
- Issue published online: 20 DEC 2001
- Article first published online: 20 DEC 2001
- Received July 3, 2000; revised manuscript received October 10, 2000; accepted October 12, 2000.
- 5-HT1A receptor;
- 5-HT1B receptor;
- 6-OHDA-lesioned rat;
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-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) and the selective 5-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.