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1 Neuroscience, PBRC-LSU system, Baton Rouge, Louisiana, United States
* To whom correspondence should be addressed. E-mail: alberto.travagli{at}pbrc.edu.
We have shown recently that cholecystokinin octapeptide (CCK-8s) increases glutamate release from nerve terminals onto neurons of the nucleus tractus solitarius pars centralis (cNTS). The effects of CCK-8s on gastrointestinal-related functions have, however, been attributed almost exclusively to its paracrine action on vagal afferent fibers. Since it has been reported that systemic or perivagal capsaicin pretreatment abolishes the effects of CCK-8s, the aim of the present work was to investigate the response of cNTS neurons to CCK-8s in vagally deafferented rats. In surgically deafferented rats, intraperitoneal administration of 1 or 3µg/kg CCK-8s increased c-Fos expression in cNTS neurons (139 and 251 % of control, respectively), suggesting that CCK-8s effects are partially independent of vagal afferent fibers. Using whole cell patch clamp techniques in thin brainstem slices, CCK-8s increased the frequency of spontaneous and miniature excitatory postsynaptic currents in 43% of the cNTS neurons via a presynaptic mechanism. In slices from deafferented rats, the percentage of cNTS neurons receiving glutamatergic inputs responding to CCK-8s decreased by approximately 50%, further suggesting that central terminals of vagal afferent fibers are not the sole site for the action of CCK-8s in the brainstem. Taken together, our data suggest that the sites of action of CCK-8s include the brainstem, and in cNTS the actions of CCK-8s are not restricted to vagal central terminals but that non-vagal synapses are also involved.
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