NIH study in rodents identifies a pathway that
starts with glutamate and ends with activation of
dopamine reward system.
Details of the role of glutamate, the brain’s
excitatory chemical, in a drug reward pathway have
been identified for the first time.
Partial view of labelled neurons in reward circuitry
that starts in dorsal raphe (pictured — ventral
tegmental area). Image courtesy Dr. Marisela Morales,
NIDA IRP
This discovery in rodents — published today in
Nature Communications — shows that stimulation of
glutamate neurons in a specific brain region (the
dorsal raphe nucleus) leads to activation of
dopamine-containing neurons in the brain’s reward
circuit (dopamine reward system).
Dopamine is a neurotransmitter present in regions of
the brain that regulate movement, emotion,
motivation, and feelings of pleasure.
Glutamate is a neurotransmitter whose receptors are
important for neural communication, memory
formation, and learning.
The research, conducted at the Intramural Research
Program (IRP) of the National Institute on Drug
Abuse (NIDA), which is part of the National
Institutes of Health, focused on the dorsal raphe
nucleus, which has long been a brain region of
interest to drug abuse researchers, since nerve
cells in this area connect to part of the dopamine
reward system.
Many of the pathways are rich in serotonin, a
neurotransmitter linked to mood regulation. Even
though electrical stimulation of the dorsal raphe
nucleus promotes reward-related behaviors, drugs
that increase serotonin have low abuse potential.
As a result, this region of the brain has always
presented a seeming contradiction, since it is
involved in drug reward but is also abundant in
serotonin - a chemical not known for a role in drug
reinforcement.
This has led researchers to theorize that another
neurotransmitter may be responsible for the role
that the dorsal raphe nucleus plays in reward.
“We now have strong evidence of a reward pathway
that starts with stimulation of glutamate neurons in
the dorsal raphe nucleus and ends in activation of
the dopamine reward system,” said NIDA Director Dr.
Nora D. Volkow. “These findings help us better
understand the brain’s reward circuitry and opens up
new avenues of research into the neurobiology of
drug addiction.”
In these rodent models, researchers used special
tracers and labelling compounds to confirm that this
circuit in the reward pathway begins with glutamate
cells in the dorsal raphe nucleus that connect to
dopamine cells in the ventral tegmental area, which
in turn travel to the nucleus accumbens, a brain
structure linked to motivation, pleasure, and
reward.
After verifying the pathway, investigators used
optogenetic techniques (using light to control
activity of modified cells) and chemical blockers to
confirm that glutamate, not serotonin, is
responsible for activating this reward circuitry.
“This glutamatergic pathway is the first fully
characterized link between electrically stimulated
reward circuitry and the dopamine system on which it
depends,” said Dr. Marisela Morales, NIDA IRP
scientist and senior author on the paper. “The
discovery of this specific brain pathway opens new
avenues to examine its participation in a variety of
disorders related to motivation.”
See also
Study shows how two brain areas interact to trigger
divergent emotional behaviors (2013-05-10)
Link...
Glutamate could contribute to restless legs syndrome
and to poor sleep (2014-06-27)
Link...
Glutamate neurotransmission system may be involved
with depression risk (15/11/2012)
Link...
Experimental drug eases depression rapidly in test
(11/12/2012)
Link...
The stressed synapse: the impact of stress and
glucocorticoids on glutamate transmission
(09/01/2012)
Link...
For more information:
The paper by Qi et al.
Link...
For similar research
currently being conducted by NIDA IRP in this area,
go to:
Link...
MDN |