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Inhibition of A9 and A10 dopamine cells by the cholecystokinin‐B antagonist LY262691: Mediation through feedback pathways from forebrain sites
Author(s) -
Rasmussen Kurt,
Howbert J. Jeffry,
Stockton Marsha E.
Publication year - 1993
Publication title -
synapse
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.809
H-Index - 106
eISSN - 1098-2396
pISSN - 0887-4476
DOI - 10.1002/syn.890150202
Subject(s) - nucleus accumbens , dopamine , medicine , chemistry , ventral tegmental area , prefrontal cortex , endocrinology , substantia nigra , medial forebrain bundle , putamen , microinjection , neuroscience , biology , striatum , dopaminergic , cognition
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 (Al0) 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 LY 262691 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. Microinjection of a structurally related CCK‐A antagonist (LY219057) into the n. accumbens or medial prefrontal cortex did not affect the number of spontaneously active A10 DA cells, and microinjection of LY219057 into the caudate‐putamen did not affect the number of spontaneously active A9 DA cells. These results indicate that, consistent with known feedback pathways between forebrain structures and midbrain DA neurons, the effects of LY262691 on A9 cells are mediated, at least in part, by antagonism of CCK‐B receptors in the caudate‐putamen, whereas the effects of LY262691 on A10 cells are mediated, at least in part, by antagonism of CCK‐B receptors in the n. accumbens and medial prefrontal cortex. © 1993 Wiley‐Liss, Inc.