Scientists at the University of Maryland School of Medicine have for
the first time found direct causal links between a key brain chemical
and avoidance-behavior related to pain and fear.
Researchers have long known that the neurotransmitter dopamine plays a
key role in driving behavior related to pleasurable goals, such as
food, sex and social interaction. In general, increasing dopamine boosts
the drive toward these stimuli. But dopamine’s role in allowing
organisms to avoid negative events has remained mysterious.
The new study establishes for the first time that dopamine is central
in causing behavior related to the avoidance of specific threats. The
work was published in the journal Current Biology.
“This study significantly advances what we know about how dopamine affects aversively motivated behaviors,” said Joseph F. Cheer PhD, a professor in the UMSOM Department of Anatomy & Neurobiology
and the study’s corresponding author. “In the past, we thought of
dopamine as a neurotransmitter involved in actions associated with the
pursuit of rewards. With this new information we can delve into how
dopamine affects so many more kinds of motivated behavior.”
To better understand the role that dopamine plays in this process, Dr. Cheer and his colleagues, including principal author Jennifer Wenzel, PhD,
a fellow in Dr. Cheer’s laboratory, studied rats, focusing on a
particular brain area, the nucleus accumbens. This brain region plays a
crucial role in linking the need or desire for a given reward – food,
sex, etc. – with the motor response to actually obtain that reward.
To study the animals under natural conditions, they used
optogenetics, a relatively new technique in which specific groups of
neurons can be controlled by exposure to light. In this case, Dr.
Cheer’s group used a blue laser to stimulate genetically modified rats
whose dopamine neurons could be controlled to send out more or less
dopamine. In this way, they were able to see how dopamine levels
affected the animals’ behavior. The principal advantage of this
approach: he could control dopamine levels even as the animals moved
freely in their environment.
The researchers subjected the animals to small electric shocks, but
also taught the animals how to escape the shocks by pressing a small
lever. Using optogenetics, they controlled the amount of dopamine
released by neurons in the nucleus accumbens. Animals with high levels
of dopamine in this brain region learned to avoid a shock more quickly
and more often than animals that had a lower level of dopamine in this
region.
Dr. Cheer says that this indicates that dopamine causally drives
animals to avoid unpleasant or painful situations and stimuli. The
results greatly expand the role that dopamine plays in driving behavior.
The researchers also examined the role that endocannabinoids play in
this process. Endocannabinoids, brain chemicals that resemble the active
ingredients in marijuana, play key roles in many brain processes. Here,
Dr. Cheer and his colleagues found that endocannabinoids essentially
open the gate that allows the dopamine neurons to fire. When the
researchers reduced the level of endocannabinoids, the animals were much
less likely to move to avoid shocks.
Dr. Cheer argues that the research sheds light on brain disorders
such as post-traumatic stress disorder and depression. In depression,
patients feel unable to avoid a sense of helplessness in the face of
problems, and tend to ruminate rather than act to improve their
situation. In PTSD, patients are unable to avoid an overwhelming sense
of fear and anxiety in the face of seemingly low-stress situations. Both
disorders, he says, may involve abnormally low levels of dopamine, and
may be seen on some level as a failure of the avoidance system.
In both depression and PTSD, doctors already sometimes treat patients
with medicine to increase dopamine and there are now clinical trials
testing use of endocannabinoid drugs to treat these conditions. Dr.
Cheer suggests that this approach may need to be used more often, and
should certainly be studied in more detail.
“Using optogenetics to understand the brain is quite revolutionary,” said E. Albert Reece, MD, PhD, MBA,
Executive Vice President for Medical Affairs at UM Baltimore, and the
John Z. and Akiko K. Bowers Distinguished Professor and Dean, University
of Maryland School of Medicine. “This research holds the potential to
elucidate questions that we have long wanted to answer about human
behavior and human mood disorders. It is not only fascinating on a
scientific level, it has potentially powerful clinical implications.”
But all this talk of genetically modified insects delivering “payloads” sounds disturbing to Silja Voeneke at the University of Freiburg, in Germany.
Her specialty is international law, including the Biological Weapons Convention, which the United States ratified in 1975. The BWC bans the use of living organisms such as bacteria or viruses as weapons of war.
Under this convention, she says, “each state party undertakes never, under any circumstances — never! under any circumstances! — to develop biological agents that have no justification for peaceful purposes,” she says.
