What is the Relationship Between Dopamine, Norepinephrine, Glutamate, and ADHD?

It does not seem that long ago that most ADHDcognitive function and physiology through intracellular
research was looking primarily at the roles of thesignaling mechanisms." The lab helped Shire
neurotransmitters dopamine and norepinephrine inPharmaceuticals in the development of Intuniv for
focus, concentration, self-control, and ADHD. But sinceADHD treatment.
one-third of the neurotransmitters in the brain areThe Arnsten Lab has been able show how the
glutamate, and brain research is now looking at therelationship between dopamine and norepinephrine and
intricate relationships between glutamate, dopamine,the ratios of dopamine to norepinephrine, can impact
and norepinephrine in the functioning of the pre-frontaland improve cognitive functions such as focus,
cortex.memory, and attention. Too much or too little of either
Research is revealing that the glutamate networkneurotransmitter decrease cognitive functions, both in
neurotransmissions from the pre-frontal cortex toterms of the performance of brain cells, and in real
other areas of the brain are more important thanworld behaviors and performance. But when the ratios
previously thought, and that they are enhanced byand relationships are just right, performance is
dopamine and norepinephrine. Too little dopamine orimproved.
norepinephrine is a problem, and too much is a problem.Their work, along with the work of many others, is
The importance of glutamate in PFC functioning isoften focused on the a2-receptor sites in the
beginning to come to the forefront in research.pre-frontal cortex. These researchers have reported
Neuro-science is beginning to move away from seeingon the benefits of norepinephrine at these PFC
ADHD as just a problem with dopamine and/orreceptor sites, and have also shown the benefits of
norepinephrine, and is moving toward a betterstimulating these receptor sites with the medication
understanding of the brain as a network with networksguanfacine (intuniv). It appears that guanfacine
of relationships such as the relationship betweenimproved cognitive functioning in the pre-frontal cortex.
dopamine, norepinephrine, the glutamate excitatoryIn addition, the research of Craig Berridge and his team
neurotransmitters which are about 30-35% of allat the University of Wisconsin-Madison has focused
neurotransmitters in the brain, and their relationship toon the effects of stimulants on the brain. He has
ADHD.shown that the main effects of stimulants are on the
In this newer framework of understanding the PFCfrontal lobes of the brain, and that small doses of
and ADHD, the new medication Intuniv from Shire hasmethylphenidate actually impact the effects of
caused a bit of a buzz. It seems that Intuniv enhancesnorepinephrine in the pre-frontal cortex more than they
the glutamate in the PFC. This is a new approach toimpact the effects of dopamine in the PFC, though
ADHD treatment.both are enhanced. This research has also shown that
Amy Arnsten, Ph.D., is the Director of the Arnsten Lab,when the a2 receptors in the pre-fronatal cortex are
Dept or Neurobiology at Yale University. According toblocked that the symptoms of ADHD can be created
its website, the Arnsten Lab "studies molecularin a subject, including lack of self-control, impulsivity, and
influences on the higher cognitive functions of thehyperactivity (Berridg et al, 2006).
prefrontal cortex (PFC), with the overarching goal ofAll of this new understanding of the effects of
developing rational treatments for cognitive disordersneurotransmitters in the pre-frontal cortex, and the
and mental illness... Research has focused on how theimpact of medications on the PFC, will help future
catecholamines norepinephrine (NE) and dopamineresearch on new medication treatments to help
(DA), powerfully and dynamically modulate PFCchildren and adults who suffer from ADHD.