Scientists identify connection between dopamine and behavior related to pain and fear

New research illuminates crucial links between avoidance behavior and key brain chemicals

April 19, 2018

Science Daily/University of Maryland School of Medicine

Scientists at the University of Maryland School of Medicine have for the first time found direct causal links between the neurotransmitter dopamine and avoidance -- behavior related to pain and fear.

Researchers have long known that 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 today in the journal Current Biology.

"This study really 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.

https://www.sciencedaily.com/releases/2018/04/180419131108.htm

How the brain suppresses pain during times of stress

March 6, 2013

Science Daily/National University of Ireland, Galway

New findings about how the brain functions to suppress pain have been published in the leading journal in the field Pain, by National University of Ireland Galway (NUI Galway) researchers. For the first time, it has been shown that suppression of pain during times of fear involves complex interplay between marijuana-like chemicals and other neurotransmitters in a brain region called the amygdala.

The work was carried out by Dr David Finn and his research team in Pharmacology and Therapeutics, Centre for Pain Research and Galway Neuroscience Centre at the National Centre for Biomedical Engineering Science, NUI Galway. The research builds on previous breakthrough findings from Dr Finn's research group on the role of marijuana-like chemicals in the brain's hippocampus in pain suppression during fear.

Pain is both a sensory and an emotional experience and is subject to modulation by a number of factors including fear and stress. During exposure to a high-stress environment or stimulus, pain transmission and perception can be potently suppressed. This important survival response can help us cope with or escape from potentially life-threatening situations. One brain region that is integral to the processing and expression of both emotional responses and pain is the amygdala.

Working with Dr Finn, first author Dr Kieran Rea was able to confirm the amygdala as a key brain region in the suppression of pain behaviour by fear (so-called fear-induced analgesia). Fear-induced analgesia was associated with increases in levels of marijuana-like substances known as endocannabinoids in the amygdala.

Furthermore, fear-induced analgesia was prevented by injecting a drug that blocked the receptor at which these endocannabinoids act into the amygdala. Further experimentation revealed that these effects involved an interaction between endocannabinoids and the classical neurotransmitters GABA (Gamma-amino butyric acid) and glutamate. An increased understanding of the biological mechanisms involved in fear-induced analgesia is important from a fundamental physiological perspective and may also advance the search for new therapeutic approaches to the treatment of pain.

Dr David Finn, Leader of the Galway Neuroscience Centre, Co-Director of the Centre for Pain Research at NUI Galway and study leader says: "The body can suppress pain when under extreme stress, in part through the action of marijuana-like substances produced in the brain. This research provides information on the complex interactions between multiple neurotransmitter systems including endocannabinoids, GABA and glutamate in times of stress and pain. This research which was funded by a grant from Science Foundation Ireland, advances our fundamental understanding of the neurobiology of pain and may facilitate the identification of new therapeutic targets for the treatment of pain and anxiety disorders."

https://www.sciencedaily.com/releases/2013/03/130306134014.htm