The new study from the Institute of Mental Health (ZI) in Mannheim, the German Cancer Research Centre (DKFZ) in Heidelberg and the University of Geneva, Switzerland suggests that cocaine induced molecular changes in connection points in the brain develops addiction to drug.
Addiction leaves detectable traces in particular brain regions including 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 following which modified synapse becomes able to transmit nervous signals with enhanced strength - a phenomenon that has been termed 'drug-induced synaptic plasticity'.
It has long been believed that drug-induced synaptic plasticity plays a crucial role in addiction development.
The research team led by Professor Dr. Gunther Schutz at the German Cancer Research Centre (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.
They studied the changes in physiology and behaviour of the genetically modified animals.
At first, both genetically modified and control animals displayed the usual behaviour under the influence of cocaine.
When they were forced to increase their agility, the 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 behaviour and preference for the cocaine-associated places subside.
However, among animals, whose receptor subunit GluR1 has been switched off, they invariably frequent the places where they expect to find the drug, i.e., their addictive behaviour persists.
Mice whose NR1 protein has been switched off have surprised scientists with a different conspicuous behaviour. If control animals withdrawn from cocaine are readministered the drug after some time, addictive behavior and drug seeking are reactivated.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 behavioural patterns," said Gunther Schutz.
"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," added Rainer Spanagel, co-investigator, from Central Institute of Mental Health (Zentralinstitut fr Seelische Gesundheit, ZI) in Mannheim.