Study reveals impacts of addiction on the brain
European researchers have shed new light on the molecular changes that take place in the brains of drug addicts. The findings could lead to the development of new treatments to wean addicts off drugs and prevent relapse. The work, which was partly funded by the EU, is published in the journal Neuron. Addiction causes molecular changes in the brain, most notably in the regions that release dopamine, a messenger molecule involved in reward-seeking behaviours. The neurons of drug addicts are modified in such a way that they can transmit much stronger dopamine signals than normal. This phenomenon is known as 'drug-induced synaptic plasticity', and researchers have suspected for many years that it plays a pivotal role in addiction development. In this latest piece of research, scientists in Germany, Switzerland and Spain studied genetically engineered mice in which certain key proteins in the dopamine-producing neurons had been switched off. The behaviour of these genetically modified mice was compared with that of ordinary mice in a series of tests. At first, the two groups behaved in a similar way: when under the influence of cocaine, the mice displayed typical, addiction-related behaviours, invariably spending most of their time in areas where they expected to find the drug. When the drugs were withdrawn, the normal mice eventually stopped looking for the drugs as their addictions subsided. However, mice in which a protein called CluR1 had been switched off continued to search for the drugs long after they had been withdrawn. In other words, their addictive behaviour persisted. In normal mice with a previous history of addiction, if cocaine is withdrawn and then re-administered after a long break, the addiction is immediately re-ignited and drug-seeking behaviours are reactivated. However, the current study found that mice lacking the protein NR1 resisted relapsing into addictive behaviours. 'It is fascinating to observe how individual proteins can determine addictive behavioural patterns,' commented Günther Schütz of the German Cancer Research Center. 'In addition, our results open up whole new prospects for treating addiction,' added Rainer Spanagel of Germany's Central Institute of Mental Health. 'Thus, blocking the NR1 receptor might protect [them] from relapsing into addiction. Selective activation of GluR1 would even contribute to 'extinguishing' the addiction.' EU support for the research came from the PHECOMP ('Phenotypical characterisation of animal models for neuropsychiatric disorders related to compulsive behaviour') project, which is financed under the 'Life sciences, genomics and biotechnology for health' Thematic area of the Sixth Framework Programme (FP6).