• 5-HT1A receptor;
  • 5-HT1B receptor;
  • l-DOPA;
  • dopamine;
  • 6-OHDA-lesioned rat;
  • microdialysis

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.