Dopamine:  A Transmitter of Motion and Motivation

Margaret E. Rice, Ph.D. Department of Neurosurgery

Department of Physiology and Neuroscience

Druckenmiller Celebration, 21 October 2009

Stock Whizzes Born Not Made, With Right Dopamine Gene

By Rob WatersOct. 2009 (Bloomberg) -- People who excel at making snap decisions and learn quickly from their mistakes, skills tied to successful stock traders, may share a genetic secret, according to a study by German neuroscientists.

These talents have been linked in research to people who carry two copies of a gene variant, called VAL, that influences the actions of the brain chemical dopamine, according to scientists at the Max Planck Institute for Human Development in Berlin. Their report was published today in the Proceedings of the National Academy of Sciences.

Stock Whizzes Born Not Made, With Right Dopamine Gene

By Rob WatersOct. 2009 (Bloomberg) -- People who excel at making snap decisions and learn quickly from their mistakes, skills tied to successful stock traders, may share a genetic secret, according to a study by German neuroscientists.

These talents have been linked in research to people who carry two copies of a gene variant, called VAL, that influences the actions of the brain chemical dopamine, according to scientists at the Max Planck Institute for Human Development in Berlin. Their report was published today in the Proceedings of the National Academy of Sciences.

PNAS October 20, 2009 vol. 106 no. 42 17951–17956

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Stock Whizzes Born Not Made, With Right Dopamine Gene http://bit.ly/xTxSX $$ - alea

Frontal cortex Cognition Working memory Schizophrenia Depression

Striatum Motion Motor learning Parkinson’s Dystonia Tourette’s

Substantia nigra - SNc

Nucleusaccumbens Motivation, reward Addiction (cocaine, amphetamine, nicotine, food, gambling)

Midbrain

Ventral tegmental area - VTA

Human midbrainSubstantia nigra (SNc)

Parkinson’s disease

PathophysiologyPrimary: loss ofSNc DA

neurons

Control Parkinson’s

Nigrostriatal dopamine pathway…

SNc

Striatum

Michael J. FoxMuhammad Ali Pope John Paul II

Janet RenoKatherine Hepburn

Why do dopamine neurons die in Parkinson’s disease?

Genetic?

Toxin/pesticide exposure?

Oxidative stress?

Mitochondrial dysfunction?

Rotenone

Powerhouse of cells

Tying these together:

Hydrogen peroxide (H2O2, an oxidant) is a surprising inhibitor of nigrostriatal DA neurons and DA release

Produced in nigral DA neurons

Generated from oxygen metabolism in mitochondria

Uncontrolled peroxide production with

rotenone exposureFuture goals:Identify therapeutic targets in Parkinson’s

• Inhibit peroxide generation• Amplify peroxide breakdown

Examine peroxide regulation in genetic models of PD