Introduction 
Reinhard Grzanna and Roger M. Brown 
A major goal in drug abuse research is to determine the neurobiological 
mechanisms by which drugs of abuse produce tolerance, dependence, 
and addiction. These behavioral manifestations of drug abuse have been 
attributed to longlasting neuroadaptations in central nervous system (CNS) 
neurons. The nature and extent of these neuroadaptations remain to be 
characterized, but investigators agree that they are the result of drug-induced 
alterations in neuronal gene expression. 
The recent discovery that cocaine and amphetamine rapidly and transiently 
induce immediate early genes (lEGs) provided the most direct indication 
that drugs of abuse can profoundly influence gene expression. Following 
their description a few years ago, lEGs and their protein products became 
recognized as important links by which extracellular signals can produce 
alterations in gene transcription. Turning on IEG expression by drugs of 
abuse may be the initial step by which drugs alter the expression of late 
genes to produce longlasting changes in neuronal functions. Thus, studies 
of the effects of drugs of abuse on lEGs may hold the key to providing the 
answer to how drugs of abuse produce long-term changes in neurons. 
Studies of this class of genes also should provide a powerful approach to 
explore correlations between drug-induced changes in behavior and the 
neuronal systems in which drugs permanently alter gene expression. 
Studies of the effects of drugs of abuse on lEGs are greatly facilitated by the 
availability of methods to visualize the activity states of these genes in tissue 
sections by immunohistochemistry and by in situ hybridization histochemistry. 
This has opened a new and promising approach to define drug-induced, 
permanent changes in the CNS and to identify the neuronal circuitries in 
which they occur. 
The chapters in this volume were presented at a conference on June 3-4, 1991 , 
in Rockville, MD, organized by the National Institute on Drug Abuse. The main 
goal of this conference was to assess the potential impact of studies of lEGs in 
the field of drug abuse research. The contributors to this volume reviewed 
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