Dopamine Release in Rat Striatum: Physiological Coupling to Tyrosine Supply (original) (raw)
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Proceedings of the National Academy of Sciences, 1980
Partial, unilateral nigrostriatal lesions of varying severity were produced in rats by injecting graded doses of 6-hydroxydopamine into the substantia nigra. Formation of the dopamine metabolites dihydroxyphenylacetic acid and homovanillic acid in each surviving nigrostriatal neuron (estimated by the ratios of dihydroxyphenylacetic acid to dopamine and homovanillic acid to dopamine in the striatum) increased significantly when dopamine concentrations in striata containing lesions had been reduced to 25% or less of control values, but remained unchanged in rats with less severe lesions. These findings suggest that, in rats with severe damage of nigrostriatal dopaminergic neurons, surviving neurons increase their firing rates and accelerate dopamine synthesis and release. In rats that had lesions and enhanced striatal dopamine release, but not in rats with lesser lesions (i.e., which reduced ipsilateral dopamine concentrations by less than 75%), administration of tyrosine (250 mg/kg) ...
2000
When incubated in a tyrosine-free medium, the tissue dopamine (DA) level of rat striatal slices increased by about 921 ± 15 pmol/mg protein during 90 min of preincubation. In contrast, the tissue-free tyrosine level declined only 130 pmol/mg protein in the same assay period. Depolarization of the slices with high K + increased both DA and DOPAC outputs and depleted tissue DA level by about 75%. Although 60 min of resting after high K + depolarization significantly restored the tissue DA levels, neither this restoration nor depolarization-induced DA release was altered by exogenous tyrosine. Similarly, failure of exogenous tyrosine was also observed during three successive depolarization periods of striatal slices. These results indicate that nigrostriatal dopaminergic neurons are able to synthesize and release the DA in the absence of exogenous tyrosine in the medium. Since the free tyrosine level in the slices does not seem to be a sufficient source, it is likely that tyrosine mobilized from its bound source(s) supports the DA synthesis under in vitro experimental conditions.
Neurochemistry International, 1982
In rat striatal synaptosomes incubated with [14C]tyrosine, the evolution of t4C02, taken as a measure of dopamine synthesis, was inhibited by exogenous dopamine and by the dopaminergic receptor agonist ADTN. The inhibition was not counteracted by dopaminergic receptor antagonists (haloperidol, sulpiride, pimozide or domperidone). Instead, it was prevented by dopamine uptake blockers, suggesting that dopamine and ADTN (a substrate of the dopamine carrier) acted once inside the nerve endings and not through activation of autoreceptors on their external membrane. The dopamine uptake inhibitors nomifensine, benztropine and cocaine increased 14C0z evolution from incubated striatal synaptosomes. Depolarization with KC1 also increased dopamine synthesis and this action was potentiated when the reuptake of the released catecholamine was prevented by carrier blockers. The rate of dopamine synthesis was lowered when synaptosomal dopamine was raised upon incubation with monoamine oxidase inhibitors or with L-DOPA. The inhibition was counteracted by dopamine reuptake blockers. The data suggest that dopamine synthesis in striatal nerve endings is under the inhibitory control of the transmitter recaptured following release.
Dopamine release and metabolism in the rat striatum: An analysis by ‘in vivo’ brain microdialysis
Pharmacology & Therapeutics, 1990
Brain microdialysis studies on the mechanisms underlying dopamine release in the rat striatum provide evidence that both exocytotic and carrier-dependent processes operate in vivo. While several releasers (potassium, veratrine, amphetamine, ouabain) utilize newly synthesized stores of dopamine, tyramine is uniquely sensitive to depletion of vesicular storage by reserpine. Extracellular DOPAC is closely associated with the newly synthesized pool of dopamine and experiments with selective monoamine oxidase inhibitors suggest that DOPAC is formed mainly by MAO-A. Recent work on the two dopamine receptors suggest that release by different mechanisms may selectively activate D~ or D 2 receptor subtypes. CONTENTS I. Introduction 281 2. Exocytotic Release 281 2.1. Definition 281 2.2. Classification of dopamine-releasing agents 282 3. Nonexocytotic (Carrier-Dependent) Release 283 3.1. Definition 283 3.2. Classification of dopamine-releasing agents 284 4.
Striatal Dopamine Releasea: In Vivo Evidence for Local Initiation
Transmitter release generally is thought to occur in response to the arrival of an action potential and the consequent initiation of calcium-dependent exocytosis. Over the past two decades it has become clear that release is not governed by action potentials alone but can be influenced by local factors, including the synaptic concentration of the transmitter under investigation. Several recent observations from our research group and others have suggested that, in addition to this impulse-dependent modulation of release, there must exist an additional mechanism for transmitter release: the local triggering of release via a heterosynaptic input.
Neuropsychopharmacology, 2001
Tyrosine availability can influence dopamine (DA) synthesis in highly electrophysiologically active DAergic neurons, such as those innervating the medial prefrontal cortex (MPFC). Whether tyrosine concentrations can also affect MPFC extracellular DA concentrations, measured in vivo , is not known. Since clozapine preferentially activates mesocortical DA neurons, we posited that tyrosine administration to a clozapine-pretreated rat would enhance the clozapine-induced augmentation of MPFC extracellular DA concentrations. Tyrosine alone (25-50mg/kg IP) did not affect mesocortical or striatal extracellular DA concentrations measured by in vivo microdialysis. Given 30 minutes after clozapine (10 mg/kg), tyrosine (50 mg/kg) significantly prolonged the clozapine-induced increase in MPFC extracellular DA concentrations but had no effect in the striatum. In contrast, tyrosine (50 mg/kg) significantly prolonged the haloperidol (1 mg/kg) induced increase in striatal extracellular DA concentrations but had no effect in the MPFC. These data constitute the first in vivo evidence that administration of tyrosine can selectively potentiate the clozapine-evoked increase in mesocortical extracellular DA concentrations.
L-DOPA administration enhances exocytotic dopamine release in the rat striatum
Life Sciences, 1992
Peripheral administration of L-3,4-dihydroxyphenylalanine (L-DOPA) methylester increased extracellular levels of DOPA and dopamine (DA) in the rat striatum monitored by in vivo brain microdialysis. The increase in DA levels persisted after inhibition of DA reuptake by nomifensine. Administration of blockers of voltage-dependent Na+ (tetrodotoxin) or Ca2+ (NKY-722) channels through the dialysis membrane completely eliminated the increase in DA levels. These results demonstrate that the L-DOPA-induced DA release is exocytotic in nature and hence, derived from neurons in the striatum.