striosome/matrix compartmentation should be considered in addition to regional 
subdivisions of the striatum in assessing the neural response to psychomotor 
stimulants. 
The selectivity of these drug effects on the induction of Fos-like proteins 
extends to the cellular level (Berretta et al. 1991a, 1991b, in press). It has 
been shown by double immunostaining that amphetamine and cocaine both 
induce Fos-like proteins in striatal medium-sized neurons expressihg the 
phosphatase inhibitor DARPP-32 (dopamine and cyclic AMP [cAMP]-regulated 
phosphoprotein) (Berretta et al. 1991a, 1991b, in press). In sharp contrast, 
neither amphetamine nor cocaine induces detectable Fos-like protein in the 
enkephalin-containing neurons in the caudatoputamen, even though many of 
these neurons coexpress DARPP-32. Nor does either stimulant induce Fos 
in striatal interneurons. These experimental findings establish that when Fos- 
like protein induction does occur in the striatum in response to psychomotor 
stimulants, the induction is only in a subset of the neurons present in the 
regions of activation. As discussed below, the subset of responsive neurons 
may have special functional characteristics that are related to the behavioral 
effects of the stimulants. 
It seems highly likely that these cell-specific patterns of IEG induction by 
psychomotor stimulants are related to the differential expression of Di-like and 
D2-like dopamine receptors by striatal neurons. The D1 -selective dopamine 
receptor blocker SCH23390 blocks the induction of immunodetectable Fos-like 
protein by either amphetamine or cocaine (Graybiel et al. 1990; Young et 
al. 1991 ; Berretta et al., in press). However, this antagonist blocks 5-HT2 
receptors as well as Di-like dopamine receptors so that a role for serotonin 
in the induction is not yet to be discounted. Control experiments designed to 
test for this have so far been negative (Graybiel et al. 1990). That the Fos- 
responsive neurons are immunoreactive for DARPP-32 agrees well with the 
apparent Di-like dopamine receptor selectivity of the induction, for DARPP-32 
is considered to be a marker for cells expressing Di-like dopamine receptors 
(Walaas et al. 1983). The lack of induction in enkephalinergic striatal neurons 
also is reasonable because these neurons are known to express D2-like 
dopamine receptors (Le Moine et al. 1990) and are thought either not to 
express Di-like receptors in large numbers (Gerfen et al. 1991) or to include 
a considerable subpopulation coexpressing Di-like and D2-like receptors 
(Meador-Woodruff et al. 1991). In the latter case, the D2-like dopamine 
receptors may block the adenylate cyclase signaling pathway activated by the 
Di-like receptor activation (Stoof and Kebabian 1981; Berretta et al., in press). 
74 
