Inhibition of A9 and A10 dopamine cells by the cholecystokinin-B antagonist LY262691: mediation through feedback pathways from forebrain sites.
The diphenylpyrazolidinone cholecystokinin-B (CCK-B) antagonist LY262691 has been shown to decrease the number of spontaneously active dopamine (DA) cells in the ventral tegmental area (A10) and substantia nigra (A9) of the anesthetized rat. In the present study, we examined the localization of the receptors mediating these effects of LY262691 on A9 and A10 DA cells. In one group of anesthetized rats, the effects of systemic administration of LY262691 on the number of spontaneously active A9 or A10 DA cells was determined using extracellular, single-unit recordings after radio frequency lesions were placed in the nucleus accumbens, caudate-putamen, or medial prefrontal cortex. Lesions of the caudate-putamen blocked the effects of systemically administered LY262691 on the number of spontaneously active A9, but not A10, DA cells. Conversely, lesions of the n. accumbens blocked the effects of systemically administered LY262691 on A10, but not A9, DA cells. Lesions of the medial prefrontal cortex blocked the effects of systemically administered LY262691 on both A9 and A10 DA cells. In a separate group of anesthetized rats, the number of spontaneously active A9 or A10 DA cells was determined after LY262691 was microinjected into the n. accumbens, caudate-putamen, or medial prefrontal cortex. Microinjection of LY262691 into the caudate-putamen led to a significant decrease in the number of spontaneously active A9, but not A10, DA cells. Conversely, microinjection of LY262691 into the n. accumbens or medial prefrontal cortex led to a significant decrease in the number of spontaneously active A10, but not A9, DA cells.(ABSTRACT TRUNCATED AT 250 WORDS)
Rasmussen
K
K
Lilly Research Laboratories, Eli Lilly & Co., Lilly Corporate Center, Indianapolis, Indiana 46285.
Howbert
J J
JJ
Stockton
M E
ME
D000758:Anesthesia; D000818:Animals; D002766:Cholecystokinin / Q000008:administration & dosage / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D003342:Corpus Striatum / Q000033:anatomy & histology / Q000166:cytology / Q000187:drug effects; D004298:Dopamine / Q000502:physiology*; D005246:Feedback / Q000502:physiology; D008297:Male; D008845:Microinjections; D009434:Neural Pathways / Q000166:cytology / Q000187:drug effects; D009714:Nucleus Accumbens / Q000033:anatomy & histology / Q000166:cytology / Q000187:drug effects; D017397:Prefrontal Cortex / Q000033:anatomy & histology / Q000166:cytology / Q000187:drug effects; D016548:Prosencephalon / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D011720:Pyrazoles; D011846:Radio Waves; D051381:Rats; D017207:Rats, Sprague-Dawley; D011954:Receptors, Dopamine / Q000187:drug effects
D011720:Pyrazoles; D011954:Receptors, Dopamine; C074681:1-(4-bromophenylaminocarbonyl)-4,5-diphenyl-3-pyrazolidinone; D002766:Cholecystokinin; D004298:Dopamine