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Role of High‐Affinity Dopamine Uptake and Impulse Activity in the Appearance of Extracellular Dopamine in Striatum After Administration of Exogenous L‐DOPA
Author(s) -
Miller David W.,
Abercrombie Elizabeth D.
Publication year - 1999
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1046/j.1471-4159.1999.721516.x
Subject(s) - microdialysis , striatum , extracellular , dopamine , dopaminergic , neurochemical , neurotransmitter , chemistry , tetrodotoxin , 3,4 dihydroxyphenylacetic acid , pharmacology , endocrinology , medicine , biology , homovanillic acid , biochemistry , serotonin , receptor
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 μ M ), 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.