Effect of apomorphine on striatal synaptotagmin 7 mRNA levels in reserpinized rats.
Synaptotagmin 7 (Syt 7) is a Ca2+ sensor implicated in the regulation of membrane fusion in vesicular transport, but its precise role in neurons is still a matter of controversy. Dopaminergic drugs have been shown to modulate its expression in the striatum. Here we investigate whether dopamine receptor agonist-up-regulation of Syt 7 mRNA is specifically involved in the pathophysiological adaptations of hypersensitive striatum by analyzing other dopaminergic neurons containing brain regions. We treated rats with systemic reserpine injections that rapidly depletes dopamine throughout the brain, but leaves dopaminergic neurons spared from destruction. We analyzed the effects of apomorphine, a D1 and D2 receptor agonist on Syt 7 mRNA expression in caudate putamen, nucleus accumbens, cingulate cortex, substantia nigra compacta, ventral tegmental area and hippocampus. The treatment with reserpine resulted in akinesia, catalepsy and rigidity and up-regulation of proenkephalin and down-regulation of preprotachykinin mRNA in caudate putamen, indicating a severe depletion. By acute treatment with apomorphine proenkephalin mRNA was down-regulated and preprotachykinin mRNA up-regulated in the caudate putamen of reserpinized rats. Apomorphine increased Syt 7 mRNA levels only in striatum (caudate putamen and nucleus accumbens) of reserpinized rats, while in other brain regions it did not have such effect. The reserpinization and/or apomorphine treatment had no effect on Syt 1 mRNA expression in caudate putamen. It may be concluded, that in the striatum depleted of biogene amines, such as occurs after reserpine treatment, the up-regulation of Syt 7 could play a specific role as part of hypersensitive response to dopaminergic agonists.
Pal
Robert
R
Brain Research Laboratory, Institute of Pathophysiology, Faculty of Medicine, University of Ljubljana, Zaloska 4, 1000 Ljubljana, Slovenia.
Zivin
Marko
M
Milutinovic
Aleksandra
A
Jernej
Branimir
B
Glavan
Gordana
G
D018759:Adrenergic Uptake Inhibitors / Q000494:pharmacology*; D000704:Analysis of Variance; D000818:Animals; D001058:Apomorphine / Q000494:pharmacology*; D001522:Behavior, Animal / Q000187:drug effects; D003342:Corpus Striatum / Q000187:drug effects*; D018491:Dopamine Agonists / Q000494:pharmacology*; D004347:Drug Interactions; D004745:Enkephalins / Q000235:genetics / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D011498:Protein Precursors / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D012110:Reserpine / Q000494:pharmacology*; D050857:Synaptotagmins / Q000235:genetics* / Q000378:metabolism; D015320:Tachykinins / Q000235:genetics / Q000378:metabolism
D018759:Adrenergic Uptake Inhibitors; D018491:Dopamine Agonists; D004745:Enkephalins; D011498:Protein Precursors; D012333:RNA, Messenger; C494304:Syt7 protein, rat; D015320:Tachykinins; C044206:preprotachykinin; C029992:proenkephalin; D050857:Synaptotagmins; D012110:Reserpine; D001058:Apomorphine