Search results for "Dopamine"

Nuclear Translocation of Nuclear Transcription Factor-κB by α-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid Receptors Leads to Transcription of …

2003

We describe a new molecular mechanism of cell death by excitotoxicity mediated through nuclear transcription factor κB (NFκB) in rat embryonic cultures of dopaminergic neurons. Treatment of mesencephalic cultures with α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) resulted in a number of changes that occurred selectively in dopaminergic neurons, including persistent elevation in intracellular Ca2+ monitored with Fura-2, and a significant increase in intramitochondrial oxidation of dihydrorhodamine 123, probably associated with transient increase of mitochondrial permeability, cytochrome c release, nuclear translocation of NFκB, and transcriptional activation of the oncogenep53.…

A high-throughput chemical screen in DJ-1β mutant flies identifies zaprinast as a potential Parkinson's disease treatment

2021

AbstractDopamine replacement represents the standard therapy for Parkinson’s disease (PD), a common, chronic, and incurable neurological disorder; however, this approach only treats the symptoms of this devastating disease. In the search for novel disease-modifying therapies that target other relevant molecular and cellular mechanisms, Drosophila has emerged as a valuable tool to study neurodegenerative diseases due to the presence of a complex central nervous system, the blood–brain barrier, and a similar neurotransmitter profile to humans. Human PD-related genes also display conservation in flies; DJ-1β is the fly ortholog of DJ-1, a gene for which mutations prompt early-onset recessive P…

Genetic polymorphisms of the dopamine D2 and D3 receptor and neuroleptic drug effects in schizophrenic patients

2001

Acetaldehyde, motivation and stress: Behavioral evidence of an addictive ménage à trois

2017

Acetaldehyde contributes to alcohol’s psychoactive effects through its own rewarding properties. Recent studies shed light on the behavioral correlates of acetaldehyde administration and the possible interactions with key neurotransmitters for motivation, reward and stress-related response, such as dopamine and endocannabinoids. This mini review critically examines acetaldehyde psychoactive properties, focusing on behavioral investigations able to unveil acetaldehyde motivational effects and their pharmacological modulation in vivo. Similarly to alcohol, rats spontaneously drink acetaldehyde, whose presence is detected in the brain following chronic self-administration paradigm. Acetaldehyd…

Opioid Inhibition of Oxytocin Release, but not Autoinhibition of Dopamine Release May Involve Activation of Potassium (K+) Channels

1991

ABSTRACT Release of oxytocin (Ox) or dopamine (DA) from the isolated neural lobes or neurointermediate lobes, respectively, was evoked by high K + (30 or 45 mM). Naloxone (1-10 μmol/l) which largely enhances the impulse-induced release of Ox had no effect on Ox release evoked by 30 or 45 mM K + . In the presence of 10 mM tetraethylammonium (TEA), Ox release evoked by 30 or 45 mM K + was increased 2-3fold; nevertheless, naloxone caused a further 2-3fold increase. Barium (500 μM) and quinidine (300 μM) antagonized the effect of naloxone observed in the presence of TEA. (-)-Sulpiride (10 μM) enhanced the release of DA evoked by 30 and 45 mM K + by 94 % and 19 %, respectively. TEA enhanced the …

The neurobiological bases for the pharmacotherapy of nicotine addiction.

2007

Nicotine, the major psychoactive agent present in tobacco, acts as a potent addictive drug both in humans and laboratory animals, whose locomotor activity is also stimulated. A large body of evidence indicates that the locomotor activation and the reinforcing effects of nicotine may be related to its stimulatory effects on the mesolimbic dopaminergic function. Thus, it is now well established that nicotine can increase in vivo DA outflow in the nucleus accumbens and the corpus striatum. The stimulatory effect of nicotine on DA release most probably results from its ability to excite the neuronal firing rate and to increase the bursting activity of DA neurons in the substantia nigra pars com…

68 Ga‐Labelled Tropane Analogues for the Visualization of the Dopaminergic System

2020

Abstract The development of radiometal‐labelled pharmaceuticals for neuroimaging could offer great potential due to easier handling during labelling and availability through radionuclide generator systems. Nonetheless, to date, no such tracers are available for positron emission tomography, primarily owing to the challenge of crossing the blood–brain barrier (BBB) and loss of affinity through chelator attachment. We have prepared a variety of 68Ga‐labelled phenyltropanes showing that, through a simple hydrocarbon‐linker, it is possible to introduce a chelator onto the lead structure while maintaining its high affinity for hDAT (human dopamine transporter) and simultaneously achieving adequa…

Catalytic Reaction Mechanism in Native and Mutant Catechol- O-methyltransferase from the Adaptive String Method and Mean Reaction Force Analysis.

2018

Catechol- O-methyltransferase is an enzyme that catalyzes the methylation reaction of dopamine by S-adenosylmethionine, increasing the reaction rate by almost 16 orders of magnitude compared to the reaction in aqueous solution. Here, we combine the recently introduced adaptive string method and the mean reaction force method, in combination with the structural and electronic descriptors to characterize the reaction mechanism. The catalytic effect of the enzyme is addressed by the comparison of the reaction in the human wild-type enzyme, in the less effective Y68A mutant, and in aqueous solution. The influence of these different environments at different stages of the chemical process and th…

Reelin and CXCL12 regulate distinct migratory behaviors during the development of the dopaminergic system.

2014

The proper functioning of the dopaminergic system requires the coordinated formation of projections extending from dopaminergic neurons in the substantia nigra (SN), ventral tegmental area (VTA) and retrorubral field to a wide array of forebrain targets including the striatum, nucleus accumbens and prefrontal cortex. The mechanisms controlling the assembly of these distinct dopaminergic cell clusters are not well understood. Here, we have investigated in detail the migratory behavior of dopaminergic neurons giving rise to either the SN or the medial VTA using genetic inducible fate mapping, ultramicroscopy, time-lapse imaging, slice culture and analysis of mouse mutants. We demonstrate that…

The differentiation of the serotonergic neurons in the Drosophila ventral nerve cord depends on the combined function of the zinc finger proteins Eag…

1997

ABSTRACT The Drosophila ventral nerve cord (vNC) derives from a stereotyped population of neural stem cells, neuroblasts (NBs), each of which gives rise to a characteristic cell lineage. The mechanisms leading to the specification and differentiation of these lineages are largely unknown. Here we analyse mechanisms leading to cell differentiation within the NB 7-3 lineage. Analogous to the grasshopper, NB 7-3 is the progenitor of the Drosophila vNC serotonergic neurons. The zinc finger protein Eagle (Eg) is expressed in NB 7-3 just after delamination and is present in all NB 7-3 progeny until late stage 17. DiI cell lineage tracing and immunocytochemistry reveal that eg is required for norm…