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

In order to determine whether L-DOPA-derived extracellular dopamine (DA) in the striatum with dopaminergic denervation is affected by activation of se rotonin autoreceptors (5-HT1A and 5-HT1B receptors), we applied in vivo bra in microdialysis technique to 6-hydroxydopamine-lesioned rats and examined the effects of the selective 5-HT1A receptor agonist 8-hydroxy2-(di-n-propy lamino)tetralin (8-OH-DPAT) and the selective S-HT1B receptor agonist CGS-1 2066 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 extracel lular 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 lev els were prolonged to 150 min and 225 min after L-DOPA injection, respectiv ely. These 8-OH-DPAT-induced changes in L-DOPA-derived extracellular DA wer e antagonized by further pretreatment with WAY-100635, a selective 5-HT1A a ntagonist. 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 ex tracellular DA. Thus, stimulation of 5-HT1A but not 5-HT1B receptors attenu ated an increase in extracellular DA derived from exogenous L-DOPA. These r esults support the hypothesis that serotonergic neurons are primarily respo nsible for the storage and release of DA derived from exogenous L-DOPA in t he absence of dopaminergic neurons.