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Cocaine: How addiction develops
August 22, 2008Permanent drug seeking and relapse after renewed drug administration are typical behavioral patterns of addiction. Molecular changes at the connection points in the brain's reward center are directly responsible for this. This finding was published by a research team from the Institute of Mental Health (ZI) in Mannheim, the German Cancer Research Center (DKFZ) in Heidelberg and the University of Geneva, Switzerland, in the latest issue of Neuron. The results provide researchers with new approaches in the medical treatment of drug addiction.
Addiction leaves detectable traces in the brain: In particular regions of the central nervous system, which produce the messenger substance dopamine, the drug cocaine causes molecular restructuring processes at the synapses, the points of connection between two neurons. As a reaction to the drug, protein subunits are exchanged in specific receptor complexes. As a result, the modified synapse becomes able to transmit nervous signals with enhanced strength - a phenomenon that has been termed 'drug-induced synaptic plasticity'. Researchers have suspected for many years that drug-induced synaptic plasticity plays a crucial role in addiction development. However, this hypothesis has not yet been proven experimentally.
Using genetic engineering, researchers headed by Professor Dr. Günther Schütz at the German Cancer Research Center (Deutsches Krebsforschungszentrum, DKFZ) have now been able to selectively switch off those protein components in dopamine-producing neurons that are integrated into the receptor complexes under the influence of cocaine. Jointly with the team of Professor Dr. Rainer Spanagel at the Central Institute of Mental Health (Zentralinstitut für Seelische Gesundheit, ZI) in Mannheim and the research group of Professor Dr. Christian Lüscher at Geneva University, the Heidelberg researchers studied the changes in physiology and behavior of the genetically modified animals.
The scientists performed standardized tests to measure addictive behavior in the animals. At first sight, both the genetically modified and the control animals displayed the usual behavior under the influence of cocaine. Forced to increase their agility, the lab animals covered significantly greater running distances and preferentially frequented those places where they had been conditioned to be regularly administered the drug.
If normal mice do not find drugs at the familiar places over a longer period of time, their addictive behavior and preference for the cocaine-associated places subside. However, this is not true for animals whose receptor subunit GluR1 has been switched off: These mice invariably frequent the places where they expect to find the drug, i.e., their addictive behavior persists.
Mice whose NR1 protein has been switched off have surprised scientists with a different conspicuous behavior. If control animals withdrawn from cocaine are readministered the drug after some time, addictive behavior and drug seeking are reactivated. In contrast, NR1 deficient animals proved to be resistant to relapsing into the addiction.
"It is fascinating to observe how individual proteins can determine addictive behavioral patterns," says Günther Schütz, and his colleague Rainer Spanagel adds: "In addition, our results open up whole new prospects for treating addiction. Thus, blocking the NR1 receptor might protect from relapsing into addiction. Selective activation of GluR1 would even contribute to 'extinguishing' the addiction."
Helmholtz Association of German Research Centres
The scientists performed standardized tests to measure addictive behavior in the animals. At first sight, both the genetically modified and the control animals displayed the usual behavior under the influence of cocaine. Forced to increase their agility, the lab animals covered significantly greater running distances and preferentially frequented those places where they had been conditioned to be regularly administered the drug.
If normal mice do not find drugs at the familiar places over a longer period of time, their addictive behavior and preference for the cocaine-associated places subside. However, this is not true for animals whose receptor subunit GluR1 has been switched off: These mice invariably frequent the places where they expect to find the drug, i.e., their addictive behavior persists.
Mice whose NR1 protein has been switched off have surprised scientists with a different conspicuous behavior. If control animals withdrawn from cocaine are readministered the drug after some time, addictive behavior and drug seeking are reactivated. In contrast, NR1 deficient animals proved to be resistant to relapsing into the addiction.
"It is fascinating to observe how individual proteins can determine addictive behavioral patterns," says Günther Schütz, and his colleague Rainer Spanagel adds: "In addition, our results open up whole new prospects for treating addiction. Thus, blocking the NR1 receptor might protect from relapsing into addiction. Selective activation of GluR1 would even contribute to 'extinguishing' the addiction."
Helmholtz Association of German Research Centres
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Athletes on performance enhancers more likely to abuse alcohol, other drugs
College athletes who use performance-enhancing substances may be at heightened risk of misusing alcohol and using recreational drugs as well, according to new research in the Journal of Studies on Alcohol and Drugs.
Local health investigation sheds light on gastroschisis birth defect
Results of an investigation conducted by University of Nevada, Reno researchers, public health officials and area physicians published this week in the Archives of Pediatrics & Adolescent Medicine, indicate that Washoe County experienced a cluster of a particular birth defect, gastroschisis, during the period April 2007 - April 2008.
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.
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.
Think what you eat: Studies point to cellular factors linking diet and behavior
New research released today is affirming a long-held maxim: you are what you eat - and, more to the point, what you eat has a profound influence on the brain.
Global public health the focus of scientific conference
Counterfeit and adulterated food and drugs and advances in measurement science used to detect them emerged as key themes of the Annual Scientific Meeting (ASM) hosted by the U.S. Pharmacopeial (USP) Convention.
Computer Model Shows Changes in Brain Mechanisms for Cocaine Addicts
About 2 million Americans currently use cocaine for its temporary side-effects of euphoria, which have contributed to making it one of the most dangerous and addictive drugs in the country.
Researchers explore long-term adolescent vulnerability to drugs
As part of efforts to understand drug abuse, Georgia State University researchers are finding that adolescent rats appear to be less vulnerable to the long-term effects of withdrawal and relapse in certain types of drug use than rats that take the drugs in adulthood.
Deaths from Unintentional Injuries Increase for Many Groups
While the total mortality rate from unintentional injury increased in the U.S. by 11 percent between 1999 and 2005, far larger increases were seen in some subgroups analyzed by age, race, ethnicity and type of injury by researchers at the Johns Hopkins Bloomberg School of Public Health's Center for Injury Research and Policy.
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