Lippincott Williams & Wilkins, Inc., Philadelphia
Role of High-Affinity Dopamine Uptake and Impulse Activity in the Appearance of Extracellular Dopamine in Striatum After Administration of Exogenous L-DOPA
Studies in Intact and 6-Hydroxydopamine-Treated Rats
Article first published online: 25 DEC 2001
Journal of Neurochemistry
Volume 72, Issue 4, pages 1516–1522, April 1999
How to Cite
Miller, D. W. and Abercrombie, E. D. (1999), Role of High-Affinity Dopamine Uptake and Impulse Activity in the Appearance of Extracellular Dopamine in Striatum After Administration of Exogenous L-DOPA. Journal of Neurochemistry, 72: 1516–1522. doi: 10.1046/j.1471-4159.1999.721516.x
Abbreviations used: AADC, aromatic amino acid decarboxylase; DA, dopamine; 6-OHDA, 6-hydroxydopamine; TTX, tetrodotoxin.
- Issue published online: 25 DEC 2001
- Article first published online: 25 DEC 2001
- Parkinson’s disease;
- Aromatic amino acid decarboxylase;
Abstract: The differential behavioral and neurochemical effects of exogenous L-DOPA in animals with intact versus dopamine (DA)-denervated striata raise questions regarding the role of DA terminals in the regulation of dopaminergic neurotransmission after administration of exogenous L-DOPA. In vivo microdialysis was used to monitor the effect of exogenous L-DOPA on extracellular DA in intact and DA-denervated striata of awake rats. In intact striatum, a small increase in extracellular DA was observed after administration of L-DOPA (50 mg/kg i.p.) but in DA-denervated striatum a much larger increase in extracellular DA was elicited. Additional experiments assessed the role of high-affinity DA uptake and impulse-dependent neurotransmitter release in the effect of exogenous L-DOPA on extracellular DA in striatum. Pretreatment with GBR-12909 (20 mg/kg i.p.), a selective DA uptake inhibitor, enhanced the ability of L-DOPA to increase extracellular DA in intact striatum. However, in DA-denervated striatum, inhibition of DA uptake did not alter the extracellular DA response to L-DOPA. Impulse-dependent neurotransmitter release was blocked by the infusion of tetrodotoxin (TTX; 1 μM), an inhibitor of fast sodium channels, through the dialysis probe. Application of TTX significantly attenuated the L-DOPA-induced increase in extracellular DA observed in striatum of intact rats pretreated with GBR-12909. In a similar manner, TTX infusion significantly attenuated the increase in extracellular DA typically observed in striatum of 6-OHDA-lesioned rats after the administration of L-DOPA. The present results indicate that DA terminals, via high-affinity uptake, play a crucial role in the clearance of extracellular DA formed from exogenous L-DOPA in intact striatum. This regulatory mechanism is absent in the DA-denervated striatum. In addition, this study has shown that DA synthesized from exogenous L-DOPA primarily is released by an impulse-dependent mechanism in both intact and DA-denervated striatum. The latter result suggests an important role for a nondopaminergic neuronal element in striatum that serves as the primary source of extracellular DA formed from exogenous L-DOPA.