Ceruletide, a cholecystokinin-related peptide, attenuates haloperidol-induced increase in dopamine release from the rat striatum: an in vivo microdialysis study.
The effects of ceruletide diethylamine (CLT), a cholecystokinin (CCK)-related peptide, on the spontaneous and haloperidol (HPD)-induced release of striatal dopamine (DA) were investigated with the in vivo microdialysis method. The striatum was perfused with Ringer solution containing different concentrations of K+. (1) When the dialysis tube was perfused with 4 mM K(+)-containing Ringer solution, CLT exerted no influence on the spontaneous and HPD-induced release of DA. (2) Increasing the K+ concentration in the perfusate from 4 to 15 mM failed to change the spontaneous and HPD-induced DA release. In this perfusion condition, the HPD-induced increase in DA release was significantly attenuated by CLT. (3) Perfusion of the striatum with the 20 mM K+ significantly reduced both the spontaneous and HPD-induced output of DA. (4) Even under the condition of perfusing the dialysis tube with the 4 mM K+, CLT significantly decreased the HPD-stimulated DA release in rats given HPD alone for the first 7 days and with CLT for the last 3 days. (5) Sixty consecutive daily administrations of HPD alone markedly reduced HPD-induced DA release from the striatum perfused with the Ringer solution containing 4 mM K+. From these results, we suggest that CLT, under the appropriate depolarization, can facilitate or induce depolarization inactivation of the A9 DA cells and/or nigrostriatal DA terminals, and consequently, produce significant inhibition of HPD-induced DA release from the rat striatum.
Shionogi Research Laboratories, Osaka, Japan.
T
T
Kihara
M
M
Ikeda
A
A
Matsushita
D015102:3,4-Dihydroxyphenylacetic Acid / Q000378:metabolism; D000818:Animals; D002108:Ceruletide / Q000031:analogs & derivatives* / Q000494:pharmacology; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism*; D004298:Dopamine / Q000378:metabolism*; D006220:Haloperidol / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D007700:Kinetics; D008297:Male; D010477:Perfusion; D011188:Potassium / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains
D015102:3,4-Dihydroxyphenylacetic Acid; C032637:ceruletide diethylamine; D002108:Ceruletide; D006220:Haloperidol; D011188:Potassium; D004298:Dopamine