Abstract
Nigrostriatal (NS) dopaminergic (DA) neurons are thought to exert an inhibitory influence on striatal enkephalinergic systems through their DA D 2 receptors. In order to investigate the effects of partial lesions of the NS DA on striatal proenkephalin (PEK) and D 2 receptor mRNAs, animals were allocated to High, Intermediate, and Low rotators on the basis of amphetamine-induced rotation observed after intrastriatal injections of 6-hydroxydopamine (6-OHDA). On the ipsilateral side of the lesions, there were significant increases in PEK mRNA in the total aspect of the caudate-putamen (CPu) of the High (+204%),the Intermediate (+125%), and of the Low (+67%) rotation groups in comparison to controls; these changes correlated positively with increases in rotation rate. Unexpectedly, there were also significant increases in striatal PEK mRNA on the contralateral side although these changes were much less prominent than those observed on the side of the lesions. Conversely, only the High rotation group showed significant increases (+112%) in D 2 receptor mRNA which occurred only on the lesioned side. Interestingly, the low rotation group actually showed some non-significant decreases (−25%) on the side of the lesions. These results indicate that partial lesions of the NS DA projections are sufficient to cause substantial increases in PEK mRNA but not in D 2 receptor mRNA. These data also provide evidence that the two nigrostriatal DA projections and the systems which they modulate might be under interdependent sets of controls. Since unilateral lesions of DA neurons cause bilateral changes in striatal DA turnover, the present experiments suggest that the striatal enkephalinergic molecular machinery may actually be under a set of controls that are more complex than a simple inhibitory influence by DA acting via its D 2 receptors.
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