K. Rasmussen et al., INHIBITION OF A9 AND A10 DOPAMINE CELLS BY THE CHOLECYSTOKININ-B ANTAGONIST LY262691 - MEDIATION THROUGH FEEDBACK PATHWAYS FROM FOREBRAIN SITES, Synapse, 15(2), 1993, pp. 95-103
The diphenylpyrazolidinone cholecystokinin-B (CCK-B) antagonist LY2626
91 has been shown to decrease the number of spontaneously active dopam
ine (DA) cells in the ventral tegmental area (A10) and substantia nigr
a (A9) of the anesthetized rat. In the present study, we examined the
localization of the receptors mediating these effects of LY262691 on A
9 and A10 DA cells. In one group of anesthetized rats, the effects of
systemic administration of LY262691 on the number of spontaneously act
ive A9 or A10 DA cells was determined using extracellular, single-unit
recordings after radio frequency lesions were placed in the nucleus a
ccumbens, caudate-putamen, or medial prefrontal cortex. Lesions of the
caudate-putamen blocked the effects of systemically administered LY26
2691 on the number of spontaneously active A9, but not A10, DA cells.
Conversely, lesions of the n. accumbens blocked the effects of systemi
cally administered LY262691 on A10, but not A9, DA cells. Lesions of t
he medial prefrontal cortex blocked the effects of systemically admini
stered LY262691 on both A9 and A10 DA cells. In a separate group of an
esthetized 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 LY26
2691 into the caudate-putamen led to a significant decrease in the num
ber of spontaneously active A9, but not A10, DA cells. Conversely, mic
roinjection of LY262691 into the n. accumbens or medial prefrontal cor
tex led to a significant decrease in the number of spontaneously activ
e 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 affe
ct the number of spontaneously active A9 DA cells. These results indic
ate that, consistent with known feedback pathways between forebrain st
ructures and midbrain DA neurons, the effects of LY262691 on A9 cells
are mediated, at least in part, by antagonism of CCK-B receptors in th
e caudate-putamen, whereas the effects of LY262691 on A10 cells are me
diated, at least in part, by antagonism of CCK-B receptors in the n. a
ccumbens and medial prefrontal cortex. (C) 1993 Wiley-Liss, Inc.