Jean-Antoine Girault talks
with ScienceWatch.com and answers a few questions
about this month's Fast Breaking Paper in the field of
Pharmacology & Toxicology.
Article Title: ERK2: a logical AND gate critical
for drug-induced plasticity?
Authors: Girault,
JA;Valjent, E;Caboche, J;Herve, D
Journal: CURR OPIN PHARMACOL
Volume: 7
Issue: 1
Page: 77-85
Year: FEB 2007
* INSERM, UMR S536, F-75005 Paris, France.
* INSERM, UMR S536, F-75005 Paris, France.
* Univ Paris 06, F-75005 Paris, France.
(addresses have been truncated)
Why do you think your paper is highly
cited?
It is a review which synthesizes current knowledge and proposes a new
hypothesis. It may provide a useful framework for understanding the
physiological significance of signaling pathways in striatal neurons, in
relation to the actions of drugs of abuse.
Would you summarize the significance of your paper in
layman's terms?
"In this article we review the mode
of action of dopamine on target cells at a
molecular level..."
Animals adapt their behavior to a changing environment thanks to powerful
learning mechanisms, including reinforcement, in response to rewards.
Dopamine, a chemical released in specific brain areas by a particular group
of neurons, plays an important role in these learning mechanisms. In this
article we review the mode of action of dopamine on target cells at a
molecular level, focusing on an important enzyme named "extracellular
signal-regulated kinase" or ERK.
Recent evidence shows that activation of ERK is important for long-term
cellular alterations which underlie behavioral changes. We argue that ERK
plays an important role by detecting the simultaneous activation of neurons
that use glutamate as neurotransmitter and code information related to the
environment in which the animal exists, and of dopamine neurons which
signal a reward. We propose that this mechanism is hijacked by drugs of
abuse which artificially increase dopamine levels.
How did you become involved in this research, and were
there any problems along the way?
We have been interested in the action of dopamine for many years since it
is a central neuromodulator in the brain, which is involved in a variety of
pathological conditions in humans.
Where do you see your research leading in the
future?
We shall continue the dissection of the basic mechanism involved in
incentive learning and in its diversion by drugs of abuse as well as in
other pathological circumstances, including Parkinson's disease.
Do you foresee any social or political implications for
your research?
Since drug abuse is a widespread health problem with important societal
consequences, progress in understanding the brain mechanisms underlying
this pathology will help to fight against it with a better efficacy and
possibly discover new therapeutic strategies.
Jean-Antoine Girault, M.D., Ph.D.
Director
Institut du Fer à Moulin
INSERM and Pierre & Marie Curie University
Paris, France
Keywords: signaling pathways in striatal neurons, drugs of
abuse, dopamine, a central neuromodulator in the brain, extracellular
signal-regulated kinase, long-term cellular alterations which underlie
behavioral changes, neurons that use glutamate as neurotransmitter,
dopamine neurons which signal a reward.