The postsynaptic effects of dopamine in the striatum are mediated mainly by receptors encoded by D1, D2, and D3 dopamine receptor genes. The D1 and D2 genes are the most widely expressed in the caudate-putamen, the accumbens nucleus, and the olfactory tubercle. Several anatomical studies, including studies using in situ hybridization with oligonucleotide and cDNA probes, have suggested that D1 and D2 receptors are segregated into distinct efferent neuronal populations of the striatum: D1 in substance P striatonigral neurons and D2 in enkephalin striatopallidal neurons. In contrast, on the basis of several in vivo and in vitro studies, other authors have suggested the existence of an extensive colocalization of D1 and D2 in the same striatal neurons. Our study was undertaken in order to analyze in detail the expression of the D1 and D2 receptor genes in the efferent striatal populations, with special reference to the various striatal areas, and to yield insights into the question about D1 and D2 mRNA localization in the striatum. We have, therefore, used highly sensitive digoxigenin- and 35S-labeled cRNA probes to address this question. The present results demonstrate that the D1 and D2 receptor mRNAs are segregated, respectively, in substance P and enkephalin neurons in the caudate-putamen and accumbens nucleus (shell and core) and in the olfactory tubercle (for their largest part). A very small percentage of neurons may coexpress both genes. These results confirm that the D1 and D2 receptor genes are expressed in distinct populations of striatal efferent neurons in the normal adult rat.

Although supersensitivity of D 2 receptors is expected when parkinsonism is first apparent, the first L-dopa dose administered does not generally induce dyskinesia, but dyskinesia develops gradually over time.7 Accordingly, the D 2 /D 3 receptor agonists exert an antiparkinsonian effect with a reduced propensity to elicit dyskinesia when administered de novo in PD patients. 8 There is some evidence that D 1 messenger RNA (mRNA) levels are increased after dopaminergic treatment of the DA-depleted striatum in animal models of LID 9 ; that downstream signal transduction cascades is abnormal in LID, 10,11 including increased phosphorylation of cAMP-regulated phosphoprotein of 32kDa 12 ; and that an altered subcellular localization of D 1 receptors is involved in LID. 13 Moreover, a DA D 1 receptor agonist with proven antiparkinsonian action 14 induced LID similar to that induced by L-dopa in PD patients, 15 further suggesting that D 1 supersensitivity plays a key role in LID occurrence. Together, these observations call for a reassessment of the changes affecting D 1 and D 2 DA receptors in LID.In this study, taking advantage of a nonhuman primate (NHP) brain bank constituted to study the pathophysiology of LID, 16 we determined changes affecting D 1 and D 2 DA receptors within the striatum of four experimental groups: normal, parkinsonian, parkinsonian chronically treated with L-dopa without exhibiting dyskinesia, and parkinsonian chronically treated with L-dopa that shows overt dyskinesia. We show that LIDs are linked to a modification of both D 1 receptor expression and sensitivity of the D 1 -signaling cascade, reinforcing the hypothesis of the pivFrom the

The dopaminergic input to the frontal cortex has an important role in motor and cognitive functions. These effects are mediated by dopamine receptors both of type D1 and of type D2, although the neural circuits involved are not completely understood. We used in situ hybridization to determine the cellular localization of D1 and D2 receptor mRNAs in the rat frontal cortex. Retrograde tracing was used in the same animals to identify the main cortical efferent populations. Fluorogold was injected into the different cortical targets of the frontal cortex and sections were hybridized with D1 and D2 35S-labelled cRNA probes. D1 and D2 mRNA-containing neurons were present in all the cortical areas investigated, with greater expression in the medial prefrontal, insular and cingulate cortexes and lower expression in the motor and parietal cortexes. Neurons containing D1 mRNA were most abundant in layer VIb; they were also present in layers VIa and V of all cortical layers and in layer II of the medial prefrontal, cingulate and insular areas. Double labelling with fluorogold demonstrated that D1 mRNA was present in corticocortical, corticothalamic and corticostriatal neurons. Neurons containing D2 mRNA were essentially restricted to layer V, but only in corticostriatal and corticocortical neurons. Neither D1 nor D2 mRNA was found in corticospinal or corticopontine neurons. The present results demonstrate that D1 and D2 receptor genes are expressed in efferent cortical populations, with higher expression for D1. In spite of an overlap in some cortical layers, the expression of D1 and D2 receptor genes is specific for different categories of pyramidal neurons.