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© PhD Students Symposium 2005. All rights reserved.
Prof. Dr. Rainer Spanagel
Central Institute of Mental Health, Mannheim, Germany
Definition: Drug addiction is defined as a syndrome in which drug use pervades all life activities of the user. The life becomes governed by the drug and the addicted patient can lose social compatibility (e.g. loss of partner and friends, loss of job, crime). Behavioural characteristics of this syndrome are compulsive drug use, craving and chronic relapses which can occur even after years of abstinence. Drug addiction is a pathological behavioural syndrome that has to be strictly separated from physical dependence. An individual can be physical dependent to a drug without being addicted to it and vice versa. Transient neuroadaptive processes underlie physical dependence and tolerance to a drug whereas persistent changes within specific neuronal systems underlie addictive behaviour.
Aims: To illustrate how modern neurobiological approaches will help
identify the neurocircuits and genes involved in addictive behavior.
Background: The current disorder concept of addiction includes neurobiological foundations and neurobiological research assuming irreversible molecular and structural changes within the brain dopamine reinforcement system constituting the ``molecular and structural switch'' from controlled drug intake to compulsive drug abuse. However, those irreversible changes have so far not been identified and it is suggested that in addition to the mesolimbic dopamine system, other brain systems including the mesocortical and nigrostriatal pathways as well as their non-dopaminergic feedback-loops might be involved in addictive behavior.
Neurobiological and genetic approach: A three-step neurobiological approach is described that allows in a first step via novel animal models and imaging techniques to identify the neuroanatomical sites mediating voluntary drug intake, reinstatement of drug-seeking behavior, relapse, loss of control and drug intake despite negative consequences. In a subsequent step, forward genetic approaches including QTL-analysis and gene expression profiling are helpful in identifying so-called candidate genes. In a final step, conditional animal mutants and selective pharmacological tools are used to functionally validate candidate genes. Following this validation process, the transfer to the human situation has to be made and candidate genes have to be further verified in well phenotyped cohorts of addicted patients.