OPIATES 
First Messengers 
RECEPTORS 
H G-PROTEINS h 
Coupling Factors 
cAMP cGMP Ca 
Second Messengers 
I 
PROTEIN KINASES | 
A 
ADDICTIVE CHANCES 
IN NEURONAL FUNCTION 
FIGURE 3. Schematic illustration of the intracellular messenger pathways 
through which diverse extracellular signals, including drugs of 
abuse such as opiates, could regulate gene expression in target 
neurons. The figure illustrates two general types of mechanisms 
that could be involved. In one mechanism, opiates, through the 
regulation of second messengers and protein kinases, regulate 
the phosphorylation of a CREB-like transcription factor. This 
alters the transcriptional activity of CREB and leads to altered 
expression of specific target proteins. In the second mechanism, 
regulation of CREB phosphorylation leads to altered expression of 
a fos-like transcription factor. Altered levels of f os, in turn, lead to 
altered expression of specific target proteins. 
SOURCE: Modified from Nestler 1992. Copyright 1992 by the Society for 
Neuroscience (New York). 
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