Induction and Suppression of Proto- 
Oncogenes in Rat Striatum After 
Single or Multiple Treatments With 
Cocaine or GBR-12909 
Michael J. ladarola , Eric J. Chuang, Choh-Lun Yeung , Yin Hoo, 
Mayme Silverthorn , Jun Gu, and Gaetano Draisci 
INTRODUCTION 
Dopamine is well known as a neurotransmitter, but its concurrent role as 
a regulator of gene expression in postsynaptic neurons is just beginning to 
be fully appreciated. Alterations in gene expression are one way a neuron 
can modify its complement of expressed proteins in response to an alteration 
in synaptic input. Increases or decreases in gene expression can lead 
to corresponding changes in cellular concentrations of neuropeptides, 
neurotransmitter synthesizing enzymes, transmitter receptors, or intracellular 
targets of second messengers. Plastic modifications in the transmitter signaling 
apparatus in a key set of neurons subsequently may alter the functional status 
of entire circuits of interconnected neuronal populations. Theoretically, 
permanent or quasi-permanent alterations in behavior can result, be they 
adaptive or maladaptive. The molecular mechanisms that effect a change in 
the expression of a gene are not fully understood. However, understanding 
events at the molecular level will be an essential component for determining 
the basis of postnatal neuronal plasticity. How does the brain react to novel 
or prolonged changes in stimuli? Certainly the changes induced by chronic 
ingestion of central nervous system (CNS)-active drugs, be they abused or 
not, can be conceptualized in terms of plastic or adaptive changes. Thus, 
investigating changes in neuronal gene expression and the mechanisms 
governing gene expression following acute and chronic administration of 
abused drugs is a powerful new approach to understanding the neuromolecular 
basis for the initiation and maintenance of drug addiction. 
A longstanding precedent for studying gene expression in the context of the 
dopamine system is found in studies of chronic dopamine D2 receptor blockade 
with the antipsychotic drug haloperidol. In animals, chronic treatment with 
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