{"id":2145,"date":"2012-03-07T00:00:00","date_gmt":"2012-03-07T08:00:00","guid":{"rendered":"https:\/\/vermont.salk.edu\/news-release\/discovery-of-brains-natural-resistance-to-drugs-may-offer-clues-to-treating-addiction\/"},"modified":"2016-01-23T11:28:06","modified_gmt":"2016-01-23T19:28:06","slug":"discovery-of-brains-natural-resistance-to-drugs-may-offer-clues-to-treating-addiction","status":"publish","type":"disclosure","link":"https:\/\/www.salk.edu\/es\/news-release\/discovery-of-brains-natural-resistance-to-drugs-may-offer-clues-to-treating-addiction\/","title":{"rendered":"Discovery of brain’s natural resistance to drugs may offer clues to treating addiction"},"content":{"rendered":"

LA JOLLA, CA\u2014A single injection of cocaine or methamphetamine in mice caused their brains to put the brakes on neurons that generate sensations of pleasure, and these cellular changes lasted for at least a week, according to research by scientists at the Salk Institute for Biological Studies.\n<\/p>\n

\nTheir findings, reported March 7, 2012 in Neuron<\/em>, suggest this powerful reaction to the drug assault may be a protective, anti-addiction response. The scientists theorize that it might be possible to mimic this response to treat addiction to these drugs and perhaps others, although more experiments are required to explore this possibility.<\/p>\n

\"Michaelanne<\/p>\n

Michaelanne Munoz, UCSD graduate student and Paul Slesinger, Associate Professor, Clayton Foundation Laboratories for Peptide Biology.<\/p>\n

Imagen: Cortes\u00eda del Instituto Salk de Estudios Biol\u00f3gicos<\/p>\n<\/div>\n

“It was stunning to discover that one exposure to these drugs could promote such a strong response that lasts well after the drug has left the body,” says Paul Slesinger<\/a>, an associate professor in the Laboratorios de la Fundaci\u00f3n Clayton para la Biolog\u00eda de los P\u00e9ptidos<\/a>. “We believe this could be the brain’s immediate response to counteract the stimulation of these drugs.”<\/p>\n

\nScientists are trying to better understand the brain’s response to psychoactive drugs in hopes of finding new ways to prevent and treat addiction. This research has become especially important as the number of deaths due to drug abuse now exceeds those due to car accidents, with more than 37,000 people dying from drugs in 2009, according to the Centers for Disease Control and Prevention<\/a>. Slesinger and Christian L\u00fcscher, a long-time collaborator at the University of Geneva, have been investigating the cellular changes in the brain that occur with drug abuse.<\/p>\n

Dopamine is a primary neurotransmitter used in the brain’s reward pathway\u2014generally speaking, the activity of dopamine neurons in the reward pathway increases in response to rewards, such as sex, food and drugs. Psychostimulants, such as methamphetamine and cocaine, co-opt this pathway and alter the brain’s response to dopamine. Understanding the neuroadaptations that occur in the reward pathway in response to drugs of abuse may lead to the development of a treatment for drug addiction.<\/p>\n

Previous research has shown that use of cocaine and methamphetamine in mice enhances excitatory connections to dopamine neurons. While most research has focused on these excitatory neurons, Slesinger and his colleagues looked at neurons that inhibit dopamine transmission, and found that one injection of cocaine or methamphetamine produces a profound change in the function of these inhibitory GABA neurons. These neurons were not able to control how they fired, so they would release more than the usual amount of inhibitory neurotransmitter.<\/p>\n

“This persistent change in the inhibitory neurons occurs simultaneously with enhancement of excitatory inputs, indicating a possible compensatory mechanism that could be protective during exposure to drugs,” Slesinger says.\n<\/p>\n

The Salk researchers identified a change in the biochemical pathway in inhibitory GABA neurons that led to this protective effect. It involved a change in the activity of a protein, known as a phosphatase, which controls the levels of a receptor known to be important for controlling the electrical activity of the GABA neuron.<\/p>\n

\"nerves<\/p>\n

The left image shows GABA inhibitory neurons (labeled green) in the brain’s reward pathway.\n<\/p>\n

\nThe right panel shows electrical activity of GABA inhibitory neuron in a Saline-injected or methamphetamine (METH)-injected mouse.\n<\/p>\n

\nActivation of the GABA type B receptor normally silences electrical activity, but has no effect in a mouse 24 hours after a single injection of methamphetamine\n<\/p>\n

Image: Courtesy of Kelly Tan and Claire Padgett, Salk Institute for Biological Studies<\/p>\n<\/div>\n

“This particular pathway\u2014involving a GABA type B receptor and a particular type of potassium channel\u2014was affected by psychostimulants in these inhibitory neurons,” Slesinger says. “We noticed a dramatic reduction in the strength of this signaling pathway, which we showed was due to a decrease in the activity of the GABAB<\/sub> receptor and the potassium channel on the neuron’s membrane surface.”\n<\/p>\n

“If we could tap into this pathway\u2014enhance the ability of inhibitory neurons to control the activity of dopamine neurons\u2014we might be able to treat some types of drug addiction,” Slesinger says.\n<\/p>\n

What is not known is how long the drug response lasts\u2014this study only looked at the brains of mice at two time points, 24 hours and seven days, after drug use\u2014and why addiction ultimately develops with chronic drug use. These are questions Slesinger and his colleagues are now investigating.<\/p>\n

The study’s two lead authors are Claire Padgett, a former postdoctoral researcher in the Slesinger laboratory, and Arnaud Lalive, a doctoral student at the University of Geneva, who is working in the laboratory of Christian L\u00fcscher, also a co-author. Other participating investigators include:
\nMichaelanne Munoz, of the University of California San Diego; Stephen Moss and colleagues from Tufts University School of Medicine; Rafael Luj\u00e1n, from the Universidad de Castilla-La Mancha in Albacete, Spain; and investigators from Hokkaido University School of Medicine in Sapporo, Japan; University College in London; and AstraZeneca in Cheshire, United Kingdom. <\/p>\n

\nEl estudio fue financiado por la National Institute on Drug Abuse<\/a>, la Instituto Nacional de Trastornos Neurol\u00f3gicos y Accidentes Cerebrovasculares<\/a>, Catharina Foundation<\/a> and the Spanish Ministry of Education and Science.\n<\/p>\n

\n
\nAcerca del Instituto Salk de Estudios Biol\u00f3gicos:<\/strong><\/br>
\nEl Instituto Salk de Estudios Biol\u00f3gicos es una de las instituciones de investigaci\u00f3n b\u00e1sica m\u00e1s destacadas del mundo, donde un cuerpo docente de prestigio internacional investiga cuestiones fundamentales de las ciencias de la vida en un entorno \u00fanico, colaborativo y creativo. Centrados tanto en el descubrimiento como en la formaci\u00f3n de las futuras generaciones de investigadores, los cient\u00edficos del Salk realizan contribuciones revolucionarias a nuestra comprensi\u00f3n del c\u00e1ncer, el envejecimiento, el Alzheimer, la diabetes y las enfermedades infecciosas mediante el estudio de la neurociencia, la gen\u00e9tica, la biolog\u00eda celular y vegetal, y otras disciplinas relacionadas.\n<\/p>\n

\nLos logros del cuerpo docente han sido reconocidos con numerosos galardones, entre los que se incluyen premios Nobel y la pertenencia a la Academia Nacional de Ciencias. Fundado en 1960 por el Dr. Jonas Salk, pionero en la vacuna contra la poliomielitis, el Instituto es una organizaci\u00f3n independiente sin fines de lucro y un hito arquitect\u00f3nico.<\/p>","protected":false},"featured_media":0,"template":"","faculty":[],"disease-research":[124],"class_list":["post-2145","disclosure","type-disclosure","status-publish","hentry","disease-research-neuroscience-and-neurological-disorders"],"acf":[],"yoast_head":"\nDiscovery of brain's natural resistance to drugs may offer clues to treating addiction - Salk Institute for Biological Studies<\/title>\n<meta name=\"robots\" content=\"index, follow, max-snippet:-1, max-image-preview:large, max-video-preview:-1\" \/>\n<link rel=\"canonical\" href=\"https:\/\/www.salk.edu\/es\/news-release\/discovery-of-brains-natural-resistance-to-drugs-may-offer-clues-to-treating-addiction\/\" \/>\n<meta property=\"og:locale\" content=\"es_MX\" \/>\n<meta property=\"og:type\" content=\"article\" \/>\n<meta property=\"og:title\" content=\"Discovery of brain's natural resistance to drugs may offer clues to treating addiction - 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