Journal of Neuroscience, Vol 5, 1387-1392, Copyright © 1985 by Society for Neuroscience
Cholecystokinin-induced excitation in the substantia nigra: evidence for peripheral and central components
DW Hommer, M Palkovits, JN Crawley, SM Paul and LR Skirboll
Cholecystokinin (CCK), one of the most common brain peptides, coexists with
dopamine (DA) in neurons of the medial substantia nigra (SN). CCK has been
shown to excite these neurons following either direct iontophoretic or
systemic administration suggesting that peripherally administered CCK may
cross the blood brain barrier to act directly on nigral DA cells. However,
biochemical evidence suggests that CCK does not cross the blood brain
barrier, and several studies have shown that the behavioral and the
satiety-inducing effects of peripherally administered CCK are abolished by
vagotomy. In order to test for vagal mediation of the nigral response to
systemically administered CCK, we examined the effects of a series of
lesions to the vagal pathways on CCK-induced excitation in the SN. Neither
acute thoracic nor chronic subdiaphragmatic vagotomies had any effect on
the excitatory response of nigral DA neurons to systemically administered
CCK. High cervical spinal cord transections were similarly without effect.
In contrast, lesions of either vagal fibers in the medulla or of the
efferent pathways from the nucleus tractus solitarii, the primary sensory
nucleus of the vagus, produced significant attenuations of the nigral
effects of systemically administered CCK. However, neither lesion blocked
effects of CCK completely. We suggest that peripherally administered CCK
has two components to its excitatory action in the SN; a component probably
mediated through CCK receptors in the nucleus tractus solitarii and a
direct action on DA neurons.
