What evidence is there that alterations in transcriptional regulation occur 
following exposure to drugs of abuse? For drugs that affect dopamine and 
other biogenic amines, including cocaine and amphetamine, there is now direct 
evidence that acute drug exposure induces expression of IEG mRNAs in the 
striatum, certain sites in the limbic system, and certain cortical areas (Graybiel 
et al. 1 990; Young et al. 1 991 ; Berretta et al. 1991 a, in press; Moratalla et al. 
1991, in press, submitted for publication; Cole et al. 1990; Dilts et al. 1990; 
Grimes et al. 1990; Robertson et al. 1991). There is also evidence that 
exposure to amphetamine and cocaine elicits expression of nuclear proteins 
detected with antisera to Fos and related IEG protein products (Graybiel et al. 
1990; Young et al. 1991). Thus, transcription and/or mRNA stabilization and 
translation of IEG protein products are induced by cocaine and amphetamine. 
PSYCHOMOTOR STIMULANTS ACTIVATE lEGs IN REGIONALLY 
SPECIFIC PATTERNS 
What characteristics of the IEG induction suggest specificity in the neural 
circuits showing this response to psychomotor stimulants? First, amphetamine 
and cocaine acutely activate lEGs in different macroscopic patterns in the 
rostral caudatoputamen and also in the ventral striatum (Graybiel et al. 1990; 
Fuxe et al. 1991). Expression of Fos-like protein is concentrated more strongly 
in the striosomes than in the matrix of the rostral caudatoputamen in rats 
acutely treated with amphetamine. By contrast, acute cocaine exposure 
induces Fos-like proteins in both striatal compartments in the rostral 
caudatoputamen. Combinations of Di-like and D2-like dopamine agonists 
given in low dose (Paul et al. 1991 , in press) and chronic apomorphine 
(Grimes et al. 1990) also induce Fos-like protein expression in patterns that 
respect striosome/matrix compartments in at least parts of the dopamine- 
depleted striatum. 
These findings raise the possibility that there is differential neural activation 
of the striosomal and matrix compartments following exposure to certain 
amphetamine-like psychomotor stimulants. Such differential activation 
could contribute to differences in behavioral responses to these drugs, 
because the striosomes and matrix have different input and output connections 
(Graybiel 1990). It is not clear how these effects of acute drug treatment relate 
to the effects of chronic drug exposure. Conceivably, these patterns could 
be related to the apparently differential toxicity induced in striosome- and 
matrix-innervating nigrostriatal fibers by continuous high-dose amphetamine 
(Ryan et al. 1988). It is also interesting that the Fos-like protein induction in 
the striatum that is elicited by acute psychostimulant exposure is influenced by 
concomitant morphine treatment and that this drug interaction is also reported 
to be compartmental (Fuxe et al. 1991). All these lines of evidence suggest that 
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