for the generation of movements (Albin et al. 1989; Mitchell et al. 1989). This 
model is supported by the report that lesions of the subthalamic nucleus reverse 
akinesia in monkeys made Parkinsonian with 1-methyl-4-phenyl-1,2,3,6- 
tetrahydropyridine (MPTP)-induced lesions (Bergman et al. 1990). 
Following cocaine self-administration, there appears to be an increase in the 
relative function of striatonigral vs. striatopallidal output systems in the dorsal 
striatum, which, according to the above model, would result in a facilitation of 
movement-related behavior. Whether such alterations are directly or indirectly 
related to the effects of cocaine is unclear. A model that relates alterations in 
the relative activity of ventral striatal output systems to specific behavioral 
responses is yet to be developed. However, the present results suggest that 
although cocaine self-administration may not produce as great an imbalance in 
the output systems of the nucleus accumbens, the fact that both systems show 
elevated gene regulation indicates that normal activity in this striatal subregion 
is also altered by cocaine. 
Although it has been proposed that the differential effects of dopamine on 
striatonigral and striatopallidal neurons are mediated by the specific expression 
of D1 and D2 dopamine receptors by these two types of output neurons, 
respectively (Gerfen et al. 1990), the cocaine-induced effects reported here 
do not necessarily indicate a predominant D1 receptor-mediated response. 
In a previous study, peptide mRNA levels in striatonigral and striatopallidal 
neurons were shown to be specifically altered by D1- or D2-selective agonists, 
respectively (Gerfen et al. 1990). However, those drug treatments were 
given to animals with lesions of the nigrostriatal dopamine pathway and thus 
examined the consequence of activation mediated by one receptor type in the 
absence of the other. In animals self-administering cocaine, both types of 
dopamine receptors would presumably be activated simultaneously. In this 
circumstance, there is considerable evidence that there are complex synergistic 
interactions between D1 and D2 dopamine receptors (Carlson et al. 1985; Clark 
and White 1987; Walters et al. 1987; Wieck and Walters 1987). One 
such interaction is the synergistic effect of D1 and D2 dopamine receptors, 
which has been well documented (Carlson et al. 1985; Clark and White 1987; 
Walters et al. 1987). The cellular basis of interactions between the dopamine 
receptor subtypes has not been established, but at least three likely 
mechanisms may be postulated. First, although the majority of striatal 
projection neurons express only one of the D1 and D2 receptor subtypes, 
there may be a subset of neurons that express both. Second, there may be 
interactions between neurons expressing different receptor subtypes through 
local axon collaterals. Third, striatal interneurons may mediate interactions 
between D1- and D2-expressing neurons. An example of this type of 
interaction may involve acetylcholine modulation of D2-containing striatopallidal 
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