Locomotor-activity-induced changes in striatal levels of preprotachykinin and preproenkephalin mRNA. Regulation by the dopaminergic and glutamatergic systems.
The mechanisms by which dopaminergic and glutamatergic inputs interact to regulate striatal neuropeptide expression during physiological motor activity are poorly understood. In this work, striatal expression of preprotachykinin (PPT) and preproenkephalin (PPE) mRNA was studied by in situ hybridization in rats killed 2 h after treadmill running (36 m/min for 20 min). Treadmill running induced a significant increase in the levels of both PPT (60% increase) and PPE (90% increase) mRNA in the striatum of normal rats. The increase in the level of PPT mRNA was blocked in rats previously subjected to nigrostriatal deafferentation (i.e., 6-hydroxydopamine lesion) or pretreated with D1-receptor antagonist SCH-23390 (0.1 mg/kg), the D2-receptor antagonist eticlopride (0.5 mg/kg), or the N-methyl-D-aspartate (NMDA) glutamate receptor antagonist MK-801 (0.1 mg/kg). The running-induced increase in the level of PPE mRNA was blocked in rats pretreated with SCH-23390 or MK-801. Rats subjected to nigrostriatal deafferentation or pretreated with eticlopride showed an increase in PPE mRNA levels (around 150% and 40% increase, respectively), that was enhanced by running (around 230% and 160% increase, respectively). These results suggest that locomotor activity increases, in a NMDA receptor dependent fashion, the excitatory influence of the corticostriatal glutamatergic system on the two populations of striatal projection neurons, as reflected by increases in the levels of PPT and PPE mRNA. The results obtained after dopamine depletion or injection of dopamine receptor antagonists suggest that a concomitant increase in dopamine release may enhance PPT mRNA level in striatonigral neurons via D1 receptors, and reduce PPE mRNA level in striatopallidal neurons via D2 receptors. Additionally, levels of dopamine and glutamate may be regulated by other complex indirect mechanisms.
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Department of Morphological Sciences, Faculty of Medicine, University of Santiago de Compostela, E-15705, Santiago de Compostela, Spain.
Rodriguez-Pallares
J
J
Caruncho
H J
HJ
Labandeira-Garcia
J L
JL
D000818:Animals; D001058:Apomorphine / Q000494:pharmacology; D001552:Benzazepines / Q000494:pharmacology; D003342:Corpus Striatum / Q000378:metabolism*; D003714:Denervation; D016291:Dizocilpine Maleate / Q000494:pharmacology; D004298:Dopamine / Q000502:physiology*; D018492:Dopamine Antagonists / Q000494:pharmacology; D004745:Enkephalins / Q000096:biosynthesis* / Q000235:genetics; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology*; D018698:Glutamic Acid / Q000502:physiology*; D017403:In Situ Hybridization; D009043:Motor Activity / Q000235:genetics*; D009419:Nerve Tissue Proteins / Q000096:biosynthesis* / Q000235:genetics; D016627:Oxidopamine / Q000633:toxicity; D011498:Protein Precursors / Q000096:biosynthesis* / Q000235:genetics; D012333:RNA, Messenger / Q000096:biosynthesis*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012420:Running / Q000502:physiology; D015320:Tachykinins / Q000096:biosynthesis* / Q000235:genetics
D001552:Benzazepines; D018492:Dopamine Antagonists; D004745:Enkephalins; D018691:Excitatory Amino Acid Antagonists; D009419:Nerve Tissue Proteins; D011498:Protein Precursors; D012333:RNA, Messenger; D015320:Tachykinins; C044206:preprotachykinin; D018698:Glutamic Acid; D016291:Dizocilpine Maleate; D016627:Oxidopamine; C033660:preproenkephalin; D001058:Apomorphine; D004298:Dopamine