L-DOPA induced extracellular dopamine increases in the ventromedial hypothalamus affects food intake by chickens on a lysine-free diet

Alam, Mohammad; Yoshizawa, Fumiaki; Sugahara, Kunio

doi:10.1016/j.neulet.2011.03.053

Cited by 4 publications

(4 citation statements)

References 22 publications

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“…DOPA, Glu, and Ser were included in the study. L-DOPA is a well known medicine used to treat Parkinson's symptoms [6-8]. L-Glu is a major excitatory amino acid in vaterbrate nervous system [51].…”

Section: Resultsmentioning

confidence: 99%

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A microchip electrophoresis-mass spectrometric platform for fast separation and identification of enantiomers employing the partial filling technique

Xiao

et al. 2013

Journal of Chromatography A

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A microchip electrophoresis-mass spectrometric (MCE-MS) method was developed for fast chiral analysis. The proposed MCE-MS platform deployed a glass /PDMS hybrid microchip with an easy-to-fabricate monolithic nanoelectrospray emitter. Enantiomeric MCE separation was achieved by means of the partial filling technique. A novel chip design with an arm channel connecting to the middle of the MCE separation channel for delivering the chiral selector was tested and proven valid. Enantiomeric separation of 3.4-dihydroxyphenylalanine (DOPA), glutamic acid (Glu), and serine (Ser), the selected test compounds, were achieved within 130 s with resolution values (Rs) of 2.4, 1.1, and 1.0, respectively. The proposed chiral MCE-MS assay was sensitive and had detection limits of 43 nM for L-DOPA and 47 nM for D-DOPA. The analytical platform was well suited for studies of stereochemical preference in living cells because it integrated cell culture, sample injection, chiral separation, and MS detection into a single platform. Metabolism of DOPA in human SH-SY5Y neuronal cells was studied as a model system. On-chip incubation of SH-SY5Y cells with racemic DOPA was carried out, and the incubation solution was injected and in-line assayed at time intervals. It was found that L-DOPA concentration decreased gradually as incubation time increased while the concentration of coexisting D-DOPA remained constant. The results firmly indicated that SH-SY5Y cells metabolized L-DOPA effectively while left D-DOPA intact.

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Section: Resultsmentioning

confidence: 99%

“…One such example is 3.4-dihydroxyphenylalanine (DOPA). L-DOPA is a popular therapeutic drug to treat Parkinson's disease [6-8]. However, it's antipode, D-DOPA, is not only inactive, but also toxic [9-10].…”

Section: Introductionmentioning

confidence: 99%

A microchip electrophoresis-mass spectrometric platform for fast separation and identification of enantiomers employing the partial filling technique

Xiao

et al. 2013

Journal of Chromatography A

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“…35 In fact, it is reported that dopamine in the ventromedial hypothalamus is associated with stimulation of food intake 36. The L-dopa administration could increase the extracellular dopamine in the ventromedial hypothalamus with a restoration of food intake,37 thus contributing to maintain this aspect in equilibrium.…”

Section: Discussionmentioning

confidence: 98%

Depressive symptoms in Parkinson’s disease and in non-neurological medical illnesses

Assogna¹,

Fagioli²,

Cravello³

et al. 2013

NDT

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BackgroundPatients with neurological and non-neurological medical illnesses very often complain of depressive symptoms that are associated with cognitive and functional impairments. We compared the profile of depressive symptoms in Parkinson’s disease (PD) patients with that of control subjects (CS) suffering from non-neurological medical illnesses.MethodsOne-hundred PD patients and 100 CS were submitted to a structured clinical interview for identification of major depressive disorder (MDD) and minor depressive disorder (MIND), according to the Diagnostic and Statistical Manual of Mental Disorders, 4th edition, text revision (DSM-IV-TR), criteria. The Hamilton Depression Rating Scale (HDRS) and the Beck Depression Inventory (BDI) were also administered to measure depression severity.ResultsWhen considering the whole groups, there were no differences in depressive symptom frequency between PD and CS apart from worthlessness/guilt, and changes in appetite reduced rates in PD. Further, total scores and psychic and somatic subscores of HDRS and BDI did not differ between PD and CS. After we separated PD and CS in those with MDD, MIND, and no depression (NODEP), comparing total scores and psychic/somatic subscores of HDRS and BDI, we found increased total depression severity in NODEP PD and reduced severity of the psychic symptoms of depression in MDD PD, with no differences in MIND. However, the severity of individual symptom frequency of depression was not different between PD and CS in MDD, MIND, and NODEP groups.ConclusionAlthough MDD and MIND phenomenology in PD may be very similar to that of CS with non-neurological medical illnesses, neurological symptoms of PD may worsen (or confound) depression severity in patients with no formal/structured DSM-IV-TR, diagnosis of depressive mood disorders. Thus, a thorough assessment of depression in PD should take into consideration the different impacts of neurological manifestations on MDD, MIND, and NODEP.

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“…However, in light of the evidence that 5-HT neurons are responsible for the release of DA induced by L-DOPA, this brain region is probably not the unique target of L-DOPA’s effects. Indeed, 5-HT neurons originating from the dorsal (DR) and median (MR) raphe nuclei send widespread innervation throughout the entire brain. , Moreover, increases in DA release induced by systemic or focal application of L-DOPA have also been observed in various brain regions using single microdialysis probe implantation including the hippocampus, the entopeduncular nucleus, the substantia nigra, and the hypothalamus. , The implantation of several dialysis probes is interesting to simultaneously monitor DA extracellular levels induced by L-DOPA within multiple brain regions and to study the regional sensitivity to L-DOPA upon several neurotransmitter systems. In the next section, we review data showing how the use of a multisite microdialysis approach has shed light on the importance of extrastriatal DA release induced by L-DOPA.…”

Section: Multisite Implantation Of Dialysis Probes To Study the Regio...mentioning

confidence: 99%

Multisite Intracerebral Microdialysis to Study the Mechanism of L-DOPA Induced Dopamine and Serotonin Release in the Parkinsonian Brain

Navailles

Lagière

Contini

et al. 2013

ACS Chem. Neurosci.

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L-DOPA is currently one of the best medications for Parkinson's disease. It was assumed for several years that its benefits and side effects were related to the enhancement of dopamine release in the dopamine-depleted striatum. The use of intracerebral microdialysis combined with a pharmacological approach has led to the discovery that serotonergic neurons are responsible for dopamine release induced by L-DOPA. The subsequent use of multisite microdialysis has further revealed that L-DOPA-stimulated dopamine release is widespread and related to the serotonergic innervation. The present Review emphasizes the functional impact of extrastriatal release of dopamine induced by L-DOPA in both the therapeutic and side effects of L-DOPA. KEYWORDS: multisite intracerebral microdialysis, L-DOPA, DA and 5-HT release, 5-HT neurons, region-dependent effects, clearance mechanisms L-DOPA is the best medication for Parkinson's disease. The use of L-DOPA as a treatment for Parkinson's disease began soon after the discovery that the striatal tissue concentration of dopamine (DA) was lower in Parkinsonian patients compared to age-matched individuals.1 The efficacy of L-DOPA was improved by combination with a peripheral inhibitor of Laromatic amino acid decarboxylase (AADC) to prevent the conversion of L-DOPA into DA in the bloodstream, thus enhancing the brain penetration of L-DOPA. Although L-DOPA is highly effective in relieving motor symptoms, numerous motor and nonmotor side-effects including L-DOPA-induced dyskinesias and psychosis can gradually emerge over time.2 The functional impact of L-DOPA in the Parkinsonian brain may not be solely restricted to its ability to restore "physiological levels" of DA in the striatum. Further investigations of its mechanism of action are thoroughly needed in order to address the motor and nonmotor side-effects of L-DOPA.Intracerebral microdialysis is a powerful sampling technique used to monitor steady-state extracellular levels of neurotransmitters in vivo. This technique has helped to decipher the mechanism of action of numerous drugs and medications with respect to their action toward neurotransmitter systems. Furthermore, the development of simultaneous implantation of multiple microdialysis probes in distinct brain regions (referred to here as multisite microdialysis) has proven its strength in revealing region-dependent dynamics of neurotransmitter release in response to pharmacological challenges and the neurochemical interactions between brain regions.Here, we summarize data showing the numerous advantages of intracerebral microdialysis to decipher the diverse features of the mechanism of action of L-DOPA in the Parkinsonian brain by using both a classical neuropharmacological approach and a multisite microdialysis approach. The present Review emphasizes the effect of L-DOPA in extrastriatal brain regions and how the region-dependent pattern of DA release induced by L-DOPA through serotonergic (5-HT) neurons may be relevant to its therapeutic and/or side-effects. I. THE US...

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L-DOPA induced extracellular dopamine increases in the ventromedial hypothalamus affects food intake by chickens on a lysine-free diet

Cited by 4 publications

References 22 publications

A microchip electrophoresis-mass spectrometric platform for fast separation and identification of enantiomers employing the partial filling technique

A microchip electrophoresis-mass spectrometric platform for fast separation and identification of enantiomers employing the partial filling technique

Depressive symptoms in Parkinson’s disease and in non-neurological medical illnesses

Multisite Intracerebral Microdialysis to Study the Mechanism of L-DOPA Induced Dopamine and Serotonin Release in the Parkinsonian Brain

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L-DOPA induced extracellular dopamine increases in the ventromedial hypothalamus affects food intake by chickens on a lysine-free diet

Cited by 4 publications

References 22 publications

A microchip electrophoresis-mass spectrometric platform for fast separation and identification of enantiomers employing the partial filling technique

A microchip electrophoresis-mass spectrometric platform for fast separation and identification of enantiomers employing the partial filling technique

Depressive symptoms in Parkinson&rsquo;s disease and in non-neurological medical illnesses

Multisite Intracerebral Microdialysis to Study the Mechanism of L-DOPA Induced Dopamine and Serotonin Release in the Parkinsonian Brain

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Depressive symptoms in Parkinson’s disease and in non-neurological medical illnesses