Acute Effects of Psychomotor 
Stimulant Drugs on Gene Expression 
in the Striatum 
Ann M. Graybiel 
INTRODUCTION 
Long-term changes in behavior leading to drug addiction imply concomitant 
drug-induced changes in central nervous system (CNS) processing. 
A large body of behavioral work implicates the mesolimbic, mesostriatal, 
and mesocortical systems as potential sites for such modifiability (Carr et 
al. 1989; Koob and Goeders 1989; Koob and Bloom 1988; Kuhar et al. 
1991). At the cellular level, changes ranging from alterations in receptor 
expression and receptor interactions with intracellular signaling molecules 
by pretranslational and posttranslational modification to alterations in 
expression or activity of such molecules have been demonstrated following 
repeated drug exposure. Both presynaptic and postsynaptic changes have 
been suggested (Robinson and Becker 1986; Post and Contel 1983; Graybiel 
1990; Terwilliger et al. 1991; Beitner-Johnson and Nestler 1991). Recently, 
interest has focused also on the possibility that regulation of immediate early 
gene (IEG) expression in neurons could lie at the basis of some or many of 
these changes. 
Interest in IEG regulation as part of the cellular basis of addiction is based 
on at least two characteristics of these genes. First, lEGs are positive and 
negative regulators of the transcription of other genes and can be regulators 
of their own transcription as well (Sheng and Greenberg 1990; He and 
Rosenfeld 1991). Thus, affecting IEG transcription could start a cascade of 
further changes that could have enduring effects on CNS function. Second, 
lEGs can act as bridges between the short-term effects of transient stimuli 
impinging on cells and long-term changes resulting from these stimuli. Just 
such considerations led to the proposal that transcriptional regulation is at the 
basis of long-term memory in neural circuits (Goelet et al. 1986; Berridge 1986; 
Morgan and Curran 1989). 
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