Quantitative in situ hybridization evidence for differential regulation of proenkephalin and dopamine D2 receptor mRNA levels in the rat striatum: effects of unilateral intrastriatal injections of 6-hydroxydopamine.
Nigrostriatal (NS) dopaminergic (DA) neurons are thought to exert an inhibitory influence on striatal enkephalinergic systems through their DA D2 receptors. In order to investigate the effects of partial lesions of the NS DA on striatal proenkephalin (PEK) and D2 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 D2 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 D2 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.(ABSTRACT TRUNCATED AT 250 WORDS)
Cadet
J L
JL
Department of Neurology, Columbia University, New York 10032.
Zhu
S M
SM
Angulo
J A
JA
D000818:Animals; D001345:Autoradiography; D001483:Base Sequence; D003342:Corpus Striatum / Q000187:drug effects / Q000502:physiology*; D004745:Enkephalins / Q000235:genetics*; D007839:Functional Laterality; D005786:Gene Expression Regulation / Q000187:drug effects; D007263:Infusions, Parenteral; D008297:Male; D008969:Molecular Sequence Data; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D009693:Nucleic Acid Hybridization; D009838:Oligodeoxyribonucleotides; D015345:Oligonucleotide Probes; D009928:Organ Specificity; D016627:Oxidopamine / Q000008:administration & dosage / Q000494:pharmacology*; D010761:Phosphorus Radioisotopes; D011498:Protein Precursors / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D011954:Receptors, Dopamine / Q000235:genetics*; D017448:Receptors, Dopamine D2; D012016:Reference Values
D004745:Enkephalins; D009838:Oligodeoxyribonucleotides; D015345:Oligonucleotide Probes; D010761:Phosphorus Radioisotopes; D011498:Protein Precursors; D012333:RNA, Messenger; D011954:Receptors, Dopamine; D017448:Receptors, Dopamine D2; C029992:proenkephalin; D016627:Oxidopamine