Welcome To Iconocast

Recent News on the Keywords, morphine stops + long term + brain , Related to the Article Below:

Morphine Makes Lasting – and Surprising – Change in the Brain

Morphine stops the synapse-strengthening process in the brain known as long-term potentiation at inhibitory synapses, according to new research conducted by Brown University brain scientist Julie Kauer. In Nature, Kauer explains this startlingly persistent effect, which could contribute to addiction and may provide a target for treatments of opioid addiction. The research also supports a provocative theory of addiction as a disease of learning and memory.

PROVIDENCE, R.I. [Brown University] — Morphine, as little as a single dose, blocks the brain’s ability to strengthen connections at inhibitory synapses, according to new Brown University research published in Nature.

The findings, uncovered in the laboratory of Brown scientist Julie Kauer, may help explain the origins of addiction in the brain. The research also supports a provocative new theory of addiction as a disease of learning and memory.

Article continues below and (thank you)

“We’ve added a new piece to the puzzle of how addictive drugs affect the brain,” Kauer said. “We’ve shown here that morphine makes lasting changes in the brain by blocking a mechanism that’s believed to be the key to memory making. So these findings reinforce the notion that addiction is a form of pathological learning.”

Kauer, a professor in the Department of Molecular Pharmacology, Physiology and Biotechnology at Brown, is interested in how the brain stores information. Long-term potentiation, or LTP, is critical to this process.

In LTP, connections between neurons – called synapses, the major site of information exchange in the brain – become stronger after repeated stimulation. This increased synaptic strength is believed to be the cellular basis for memory.

In her experiments, Kauer found that LTP is blocked in the brains of rats given as little as a single dose of morphine. The drug’s impact was powerful: LTP continued to be blocked 24 hours later – long after the drug was out of the animal’s system.

“The persistence of the effect was stunning,” Kauer said. “This is your brain on drugs.”

Kauer recorded the phenomenon in the ventral tegmental area, or VTA, a small section of the midbrain that is involved in the reward system that reinforces survival-boosting behaviors such as eating and sex – a reward system linked to addiction. The affected synapses, Kauer found, were those between inhibitory neurons and dopamine neurons. In a healthy brain, inhibitory cells would limit the release of dopamine, the “pleasure chemical” that gets released by naturally rewarding experiences. Drugs of abuse, from alcohol to cocaine, also increase dopamine release.

So the net effect of morphine and other opioids, Kauer found, is that they boost the brain’s reward response. “It’s as if a brake were removed and dopamine cells start firing,” she explained. “That activity, combined with other brain changes caused by the drugs, could increase vulnerability to addiction. The brain may, in fact, be learning to crave drugs.”

Kauer and her team not only recorded cellular changes caused by morphine but also molecular ones. In fact, the researchers pinpointed the very molecule that morphine disables – guanylate cyclase. This enzyme, or inhibitory neurons themselves, would be effective targets for drugs that prevent or treat addiction.

Fereshteh Nugent, a Brown postdoctoral research associate, and Esther Penick, a former Brown postdoctoral research associate who now serves as assistant professor of biology at Knox College, rounded out the research team.

The National Institute of Drug Abuse funded the work.

Editors: Brown University has a fiber link television studio available for domestic and international live and taped interviews and maintains an ISDN line for radio interviews. For more information, call the Office of Media Relations at (401) 863-2476.

source : http://www.brown.edu/Administration/News_Bureau/2006-07/06-144.html

Morphine and other opioids are among the most potent painkillers around. For the first time, Brown University neuroscientists explain why these drugs work so well on calcium channels in the pain pathway in new research in Nature Neuroscience. The findings not only break ground in basic science, they may aid in the effort to develop safer pain-relieving drugs.

PROVIDENCE, R.I. [Brown University] — Whether they’re fighting postoperative soreness or relieving chronic discomfort from conditions such as cancer, morphine and other opioids are powerful weapons against pain. Now, in research published online in Nature Neuroscience, Brown University scientists give one reason why these painkillers work so well.

The secret: They act on a special form of N-type calcium channel, the cellular gatekeepers that help control pain messages passed between nerve cells. By blocking these channels, pain signals are inhibited. These findings not only shed important light on how the body controls pain, they could be a boon to drug development.

“We’ve known that drugs such as morphine are highly effective at blocking calcium channels, but we’ve never known precisely why – until now,” said Brown neuroscientist Diane Lipscombe, who led the research. “With this new understanding of how opioids work on calcium channels, drug companies could develop effective new painkillers.”

Lipscombe, a professor in the Department of Neuroscience, is an expert in N-type calcium channels, critical players in the pain pathway. At the synapse – the point of connection between nerve cells – N-type channels control the release of neurotransmitters. These chemicals carry messages between nerve cells – messages that include sensations of pain. So if you block N-type channels, you can block pain.

But all of these channels shouldn’t be closed, Lipscombe explained. That’s because some pain signals – “That stove is hot!” – are needed to survive. “You don’t want to shut off all pain signals,” she said. “You just want to dampen some of them down.”

In 2004, Lipscombe and her colleagues discovered a unique form of the N-type channel in nociceptors, neurons that carry pain signals to the spinal cord. These are the channels that opioids act on. But what makes the channels in nociceptors so special?

In their new work, Lipscombe and her team uncover the answer. All N-type channels are made up of a string of about 2,400 amino acids. In nociceptor N-type channels, that string differs by a mere 14 amino acids, Lipscombe and her team learned. This small difference in molecular make-up makes these channels much more sensitive to the pain-blocking action of opioids.

“In nociceptor N-type channels, you get double-barreled inhibitory action,” she explained.

Jesica Raingo, a Brown postdoctoral research fellow, is lead author of the Nature Neuroscience article. Andrew Castiglioni, a former Brown graduate student, participated in the research.

The National Institute of Neurological Disorders and Stroke funded the work.

Editors: Brown University has a fiber link television studio available for domestic and international live and taped interviews and maintains an ISDN line for radio interviews. For more information, call the Office of Media Relations at (401) 863-2476.