Effect of chronic ceruletide treatment on dopaminergic neurotransmitters, receptors and their mRNAs in the striatum of rats with dyskinesia induced by iminodipropionitrile.
To clarify the mechanism of long-lasting ceruletide action, an analogue of cholecystokinin, in relieving the dyskinesia induced by the iminodipropionitrile (IDPN), we investigated the changes in dopaminergic neuronal system in the striatum. In the control rats, ceruletide had no significant effect on the concentrations of dopamine (DA), DOPAC or HVA or on the turnover of DA in the striatum. The concentration of DA was decreased and the turnover of DA [(DOPAC + HVA)/DA] was increased in the striatum of IDPN-treated rats. Chronic administration of ceruletide (160 micrograms.kg-1.day-1 x 10 days) increased DA concentration and decreased DA turnover only transiently. Both D1 and D2 receptors and their mRNAs were decreased in the striatum of rats given IDPN. After chronic ceruletide treatment, D1 receptor rose to the control level for 3 days, while the D2 receptor rose to a level 1.5 times the control level for 3 days. Even at the 7 days after chronic ceruletide treatment, D2-R rose significantly as compared with the IDPN-treated rats. Both D1 and D2 receptor mRNAs were significantly increased for 3 days in the IDPN-treated rats. These observations indicate that the synthesis of DA receptors is increased by ceruletide treatment in the striatum of IDPN-treated rats. These changes in DA receptors and their mRNAs closely paralleled the changes in dyskinetic movement of the IDPN-treated rats after repeated daily administration of ceruletide, as previously reported. The parallel changes between the DA receptors and dyskinetic movement suggest that an up-regulation of DA receptors in the striatum corresponds with an improvement of dyskinesia in the IDPN-treated rats.(ABSTRACT TRUNCATED AT 250 WORDS)
Hirata
H
H
Department of Neuroscience, Okayama University Medical School, Japan.
Ogawa
N
N
Asanuma
M
M
Ota
Z
Z
Mori
A
A
D015102:3,4-Dihydroxyphenylacetic Acid / Q000378:metabolism; D000818:Animals; D001552:Benzazepines / Q000378:metabolism; D015152:Blotting, Northern; D002108:Ceruletide / Q000008:administration & dosage / Q000494:pharmacology*; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism*; D004298:Dopamine / Q000378:metabolism*; D004334:Drug Administration Schedule; D004409:Dyskinesia, Drug-Induced / Q000378:metabolism*; D006719:Homovanillic Acid / Q000378:metabolism; D008297:Male; D009498:Neurotoxins / Q000633:toxicity; D009570:Nitriles / Q000633:toxicity*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017447:Receptors, Dopamine D1 / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D017448:Receptors, Dopamine D2 / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D013134:Spiperone / Q000378:metabolism; D013997:Time Factors
D001552:Benzazepines; D009498:Neurotoxins; D009570:Nitriles; D012333:RNA, Messenger; D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2; D015102:3,4-Dihydroxyphenylacetic Acid; C008110:3,3'-iminodipropionitrile; D013134:Spiperone; D002108:Ceruletide; D004298:Dopamine; D006719:Homovanillic Acid