Dr. Remington Nevin has posted on Facebook tonight an interesting article that promises relief for those suffering from a reaction to mefloquine. Dr. Nevin makes this observation: “I’ve been trying to tell my Army minders for some time that mefloquine gap junction blockade might cause chronic anxiety states. Now the neurobiologists are catching up. Maybe the Army will listen now!”
This is the article in Medill Schools’s Reports out of Chicago posted January 20, 2011 –BONNIE
Traumatic experiences may soon become a thing of the past—literally.
University of California, Los Angeles researchers have discovered a new way to look at the brain, and as a result, have found that by disrupting brain patterns they are able to erase memories of fearful experiences or even prevent them from forming.
“This is a novel and important discovery about how fear works in the brain,” said Joseph LeDoux, neuroscientist and professor of neuroscience and psychology at New York University, who was not involved in the study.
Psychologist Michael Fanselow and his UCLA colleagues focused on gap junctions—tiny holes between neurons that allow electricity to pass from one neuron to another. Gap junctions are essentially spaces in the membrane separating cells from one another, an opening between nerve cells.
The junctions cause neurons to fire together, coordinating the production of fear memories. They have not been heavily researched because they are rare in mammals, but common in invertebrates.
Fanselow discovered that neurons communicate in a different way than previously understood.
Neurons are nerve cells that process and transmit information in the brain and they are critical in the formation of memory. In the brain, neurons act as “highways” that neurotransmitters travel down. Neurotransmitters, chemicals that transmit information, act as signals moving down the highway. In the past, research has shown that communication among neurotransmitters moving across synapses, the space between neurons, accounts for the stimulation of nerve cells.
The UCLA research shows that direct electrical contact between neurons plays a large part in the formation of fear.
“We discovered that this other mode of communication is important for memory, so it opens the way for new ways to treat the brain—not just for fear memories but in many conditions,” Fanselow said.
The UCLA team tested rats using Pavlovian fear conditioning—the rats received a mild electric shock after being placed in a cage. Scientists then immediately injected rats with a mix of drugs that acted as impairments to the formation of fear. These medications disrupted rhythms in the hippocampus, the part of the brain that plays a large part in the formation of memory.
Rats that had been shocked but had gap junctions blocked acted as if their cages were new.
“Human memory or animal memory is not like a computer, where you sit down and type something and it’s there,” said Gyorgy Buzsaki, a neuroscientist at Rutgers University in Newark,N.J. “It’s almost like a Polaroid picture—you take a photo and it takes time to develop. Because of this slow process with an extended vulnerable period, memories can be specifically erased.” He added that drugs, including gap junction blockers, may exploit memory vulnerability and have negative side effects.
Rats were injected with two blockers: the general gap junction blocker carbenoxolone and selective blocker mefloquine. Carbenoxolone is used for treating ulcerations and lesions. It has been proven to have negative effects on cognition and serves as a gap junction blocker. Mefloquine is used to prevent malaria and has numerous side effects in humans including anxiety, paranoia, insomnia and seizures.
But Fanselow said that many of the negative effects of mefloquine arise with chronic use. “To actually test these drugs on humans clinically is a very involved process,” Fanselow said. “I think we need to do some more research on animals to fully appreciate the costs and benefits that come with any drug treatment.”
Cheryl Carmin, director of the Stress and Anxiety Disorders Clinic at the University of Illinois-Chicago, explained that not all fear is bad. “[Many times] being anxious is an appropriate response. It’s part of our innate alarm system,” she said. “But for people with anxiety disorders, it may become a false alarm so in effect, they [researchers] can target that.”
Fanselow and his team plan to continue blocking electrical synapses in animals to see what aspects of anxiety can be affected.
Michael Davis, professor of psychiatry and behavioral sciences at the Emory University School of Medicine in Atlanta, said Fanselow’s research has vast scientific implications.
“From a purely scientific basis it’s very interesting that these gap junctions play a role in fear memory. For the clinicians, the most interesting thing would be if you could treat a memory after a trauma and speed up subsequent psychotherapy and reduce relapse,” he said.
This discovery has implications for a new drug target for treating anxiety disorders, victims of traumatic experiences and people with Alzheimer’s disease.
Because memory is impaired by diseases such as Alzheimer’s, the UCLA group plans to look at enhancing gap junctions and improving memory formation. Through finding more specific ways of manipulating gap junctions, they hope to better understand normal brain function and find the right treatment for different conditions.