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Related Concept Videos

Human Genetics01:28

Human Genetics

Human genetics provides a profound framework for understanding the interplay between genetic predispositions and human psychology. At the heart of this discipline lies the study of how genes influence physical traits, behaviors, and susceptibility to diseases. Each person carries a unique genetic code that subtly or significantly shapes their psychological and behavioral landscape.
The complex relationship between genetics and psychology is observable through common biological components such...
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Drugs Affecting Neurotransmitter Synthesis

Drugs affecting neurotransmitter synthesis can impact the adrenergic neuron and the synthesis of neurotransmitters. For example, α-methyltyrosine and carbidopa target specific enzymes involved in catecholamine synthesis. α-methyltyrosine inhibits the enzyme tyrosine hydroxylase, which converts tyrosine into dopamine. By blocking this enzyme, α-methyltyrosine reduces dopamine production and other catecholamines. Carbidopa, on the other hand, inhibits the enzyme dopa decarboxylase, which converts...
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Drugs Affecting Neurotransmitter Release or Uptake

Certain drugs can affect how neurotransmitters called catecholamines, are released or taken back up in the adrenergic neuron. They can have different effects on the body's sympathetic transmission. Reserpine, a natural compound found in the Rauwolfia shrub, blocks a transporter called vesicular monoamine transporter (VMAT), which leads to a buildup of catecholamines in the cell and reduces sympathetic transmission. Another drug called guanethidine works in multiple ways, including blocking...
Huntington Disease l: Introduction01:21

Huntington Disease l: Introduction

Huntington disease or HD is a progressive, fatal neurodegenerative disorder inherited in an autosomal dominant pattern.PathophysiologyIt is caused by expansion of the CAG trinucleotide repeat in the HTT gene on chromosome 4 (4p16.3), producing an abnormal huntingtin protein with an expanded polyglutamine tract. This misfolded protein disrupts cellular function, leading to neuronal death. Normal alleles have ≤26 repeats, 27–35 are intermediate (risk of expansion), 36–39 show reduced penetrance,...
The Significance of Membrane Transport01:44

The Significance of Membrane Transport

The transport of solutes across the cell membrane is essential for metabolic processes, like maintaining cell size and volume, generating the action potential, exchanging nutrients and gases, etc. Membrane transport can be either passive or active. It can be simple diffusion, facilitated, or mediated transport aided by transport proteins such as transporters and channels.
Transporters facilitate either an active or passive movement of solutes. They can allow a single-molecule transport down its...

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Related Experiment Video

Updated: Jul 3, 2026

Dopamine Release at Individual Presynaptic Terminals Visualized with FFNs
09:37

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Published on: August 31, 2009

Anomalous dopamine release associated with a human dopamine transporter coding variant.

Michelle S Mazei-Robison1, Erica Bowton, Marion Holy

  • 1Department of Pharmacology, Vanderbilt University Medical Center, Nashville, Tennessee 37232-8548, USA.

The Journal of Neuroscience : the Official Journal of the Society for Neuroscience
|July 11, 2008
PubMed
Summary

A rare dopamine transporter (DAT) variant, Ala559Val, causes abnormal dopamine efflux, potentially explaining attention-deficit hyperactivity disorder (ADHD). This variant

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Assessment of Dopaminergic Homeostasis in Mice by Use of High-performance Liquid Chromatography Analysis and Synaptosomal Dopamine Uptake
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Published on: June 5, 2017

Area of Science:

  • Neuroscience
  • Genetics
  • Pharmacology

Background:

  • Dopamine (DA) signaling is crucial for brain function and is regulated by release and clearance.
  • Dysregulation of DA signaling is implicated in various neurological and psychiatric disorders, including ADHD.

Purpose of the Study:

  • To investigate the functional impact of a rare human DAT (hDAT) coding variant, Ala559Val, identified in individuals with ADHD.
  • To explore the mechanism by which this variant affects DA signaling and its interaction with ADHD medications.

Main Methods:

  • Genetic analysis to identify the hDAT Ala559Val variant in a pedigree with ADHD.
  • In vitro studies using DA-loaded cells to assess DAT protein expression, DA uptake, and DA efflux.
  • Electrophysiological recordings to evaluate the variant's response to intracellular ions and membrane potential.

Main Results:

  • The hDAT Ala559Val variant supports normal DAT expression and uptake but exhibits anomalous DA efflux.
  • The variant shows increased sensitivity to intracellular Na(+) and exaggerated DA efflux at depolarized potentials.
  • Common ADHD medications, amphetamine and methylphenidate, block hDAT Ala559Val-mediated DA efflux, unlike their effects on wild-type DAT.

Conclusions:

  • A heritable change in hDAT structure can lead to DA efflux, offering a new mechanism for DA signaling disorders like ADHD.
  • The findings suggest that blocking inappropriate neurotransmitter efflux may be a therapeutic mechanism for existing transporter-directed medications.