The CCK-B antagonist CI-988 increases dopamine levels in microdialysate from the rat nucleus accumbens via a tetrodotoxin- and calcium-independent mechanism.
CI-988, a water-soluble, selective cholecystokinin-B antagonist, was perfused through a microdialysis probe into the anterior nucleus accumbens, posterior nucleus accumbens, or caudate nucleus of anesthetized rats. High concentrations of CI-988 produced three- to fivefold increases in dopamine overflow, at all three sites, that were temporally correlated with the CI-988 perfusion and returned to baseline levels upon cessation of CI-988 perfusion. However, the cholecystokinin-A antagonist CAM-1481, and the relatively inactive enantiomer of CI-988, CAM-1241, also increased dopamine overflow in the nucleus accumbens. Furthermore, the ability of CI-988 to increase dopamine overflow persisted in the absence of calcium in the perfusate and was not sensitive to tetrodotoxin treatment. The mechanism by which locally administered CI-988 increases dopamine overflow appears not to be anatomically specific, not selective for one cholecystokinin receptor subtype, and may be nonvesicular.
Corwin
R L
RL
Section on Behavioral Neuropharmacology, National Institute of Mental Health, National Institutes of Health, Bethesda, MD 20892-1380, USA.
Jörn
A
A
Hardy
M
M
Crawley
J N
JN
D000818:Animals; D002118:Calcium / Q000494:pharmacology*; D002766:Cholecystokinin / Q000037:antagonists & inhibitors*; D004298:Dopamine / Q000378:metabolism*; D018492:Dopamine Antagonists / Q000494:pharmacology*; D007211:Indoles / Q000494:pharmacology*; D008297:Male; D008536:Meglumine / Q000031:analogs & derivatives* / Q000494:pharmacology; D017551:Microdialysis; D009714:Nucleus Accumbens / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013779:Tetrodotoxin / Q000494:pharmacology*
D018492:Dopamine Antagonists; D007211:Indoles; C065599:PD 134308; D013779:Tetrodotoxin; D008536:Meglumine; D002766:Cholecystokinin; D002118:Calcium; D004298:Dopamine