The discovery of endogenous opioids has markedly influenced the research on the biology of drug dependence. Evidence has been presented that these brain substances are self-administered by laboratory animals. This finding, among others, has led to the hypothesis that endogenous opioids are involved in reinforcing habits, including dependence on drugs of abuse. The course of drug dependence is presented as a continuum from no drug use via controlled use to an actual dependence on the drug. Specific brain opioid systems belonging to four conceptualized brain circuits are described to be involved during the different phases of the drug dependence continuum. More recent research to delineate the role of endogenous opioid systems in drug dependence has focussed on genetic research in humans and animals. Among others, the findings obtained from studies of opioid receptor and opioid peptide precursor knockout mice provided further support for a role of endogenous opioid systems in drug dependence, in agreement with previous pharmacological studies.
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