Caltech scientists engineer supersensitive receptor, gain better understanding of dopamine systemOctober 15, 2008Receptor may be good target for treatment of smoking addiction, ADHD, and more PASADENA, Calif.--Genetically modifying a receptor found on the neurons that produce the neurotransmitter dopamine has given California Institute of Technology (Caltech) researchers a unique glimpse into the workings of the brain's dopamine system--as well as a new target for treating diseases that result from either too much or too little of this critical neurotransmitter. Caltech scientists Henry Lester, Bren Professor of Biology, and Ryan Drenan, senior postdoctoral scholar in biology, worked with colleagues from Caltech, the University of Colorado at Boulder, the Rockefeller University, the University of Utah, and the pharmaceutical company Targacept. They genetically modified a type of brain receptor known as an "α6-containing nicotinic acetylcholine receptor" to make it more sensitive to both nicotine and acetylcholine. (Acetylcholine is another of the brain's neurotransmitters.) The receptor in question is found primarily on neurons that produce the neurotransmitter dopamine. When the receptor is kicked into action by the presence of either nicotine or acetylcholine--two of the keys that fit its biochemical lock--the receptor prompts the neurons on which it sits to begin pumping out dopamine. While previous studies of this same receptor had shown what happens when you block its function--when you put the brakes on dopamine production--this was the first time anyone was able to look at what happens when you make the receptor more sensitive and thus put the dopamine system into overdrive. "We were able to not only isolate this receptor's function, but also to amplify it," says Drenan, "and that allowed us to see exactly what it and it alone is capable of doing in the brain." As it turns out, it's capable of doing a lot. Revved up by even low doses of nicotine, these receptors prompt the neurons on which they are clustered to let loose with a flood of dopamine. This flooding was obvious from the behavior of mice carrying the genetically modified receptors: because dopamine plays an important role in movement, the mice became quickly and significantly hyperactive. In fact, the researchers note, low doses of nicotine affect mice with these hypersensitive receptors in much the same way that amphetamines affect "normal" mice. Looking more closely at this phenomenon, the researchers write, "could be useful in understanding the causes of human hyperactivity such as that observed in ADHD." "This technique also gives researchers the power to activate dopamine neurons selectively," says Lester. "We plan to exploit this opportunity to obtain new knowledge about dopamine neurons' functions." While these sensitized receptors appear on dopamine neurons throughout the brain, the researchers note that they seem to play an especially critical role in what is called the mesolimbic pathway--one of four pathways that control dopamine production throughout the brain, and the one implicated in the addictive properties of drugs like nicotine. To this end, Lester's team and their collaborators have already begun to explore the possibilities of targeting these receptors with specific drugs that might work to reduce their sensitivity to nicotine, potentially providing a new line of attack for treating nicotine addiction. In fact, notes Drenan, these same drugs might also one day prove useful in treating other dopamine-related conditions, such as ADHD, Parkinson's disease, and schizophrenia. "By uncovering the biological role of these receptors, especially with regard to their role in the midbrain dopamine system, we show that they are excellent drug targets," says Drenan. California Institute of Technology |
|||||||||||||||||||||
| Related Dopamine Current Events and Dopamine News Articles ISU researchers' findings bring hope for possible Parkinson's disease cure Researchers at Iowa State University have found an essential key to possibly cure Parkinson's disease and are looking for others. Widely used cholesterol-lowering drug may prevent progression Simvastatin, a commonly used, cholesterol-lowering drug, may prevent Parkinson's disease from progressing further. Neurological researchers at Rush University Medical Center conducted a study examining the use of the FDA-approved medication in mice with Parkinson's disease and found that the drug successfully reverses the biochemical, cellular and anatomical changes caused by the disease. Stress-induced changes in brain circuitry linked to cocaine relapse Stress-evoked changes in circuits that regulate serotonin in certain parts of the brain can precipitate a low mood and a relapse in cocaine-seeking, based on mouse studies published online this week in the Proceedings of the National Academy of Sciences. Researchers find brain cell transplants help repair neural damage A Swiss research team has found that using an animal's own brain cells (autologous transplant) to replace degenerated neurons in select brain areas of donor primates with simulated but asymptomatic Parkinson's disease and previously in a motor cortex lesion model, provides a degree of brain protection and may be useful in repairing brain lesions and restoring function. Changes in brain chemicals mark shifts in infant learning When do you first leave the nest? Early in development infants of many species experience important transitions-such as learning when to leave the protective presence of their mother to start exploring the wider world. Why antidepressants don't work for so many More than half the people who take antidepressants for depression never get relief. Cocaine exposure during pregnancy leads to impulsivity in male, not female, monkeys Adult male monkeys exposed to cocaine while in the womb have poor impulse control and may be more vulnerable to drug abuse than female monkeys, even a decade or more after the exposure, according to a new study by researchers at Wake Forest University School of Medicine. The findings could lead to a better understanding of human drug abuse. Scientists demonstrate link between genetic defect and brain changes in schizophrenia Researchers at the University of North Carolina at Chapel Hill School of Medicine have found that the 22q11 gene deletion - a mutation that confers the highest known genetic risk for schizophrenia - is associated with changes in the development of the brain that ultimately affect how its circuit elements are assembled. Fine-tuning treatments for depression New research clarifies how neurotransmitters like norepinephrine, serotonin, and dopamine, are regulated - a finding that may help fine-tune therapies for depression. Study supports possible role of urate in slowing Parkinson's disease progression By examining data from a 20-year-old clinical trial, a research team based at the MassGeneral Institute for Neurodegenerative Diseases (MGH-MIND) and Harvard School of Public Health (HSPH), has found evidence supporting the findings of their 2008 study - that elevated levels of the antioxidant urate may slow the progression of Parkinson's disease. More Dopamine Current Events and Dopamine News Articles |
|||||||||||||||||||||
|
|||||||||||||||||||||
|
|||||||||||||||||||||