Cholecystokinin Excites Neostriatal Neurons in Rats via CCKA or CCKB Receptors

Abstract

The effect of iontophoretically applied cholecystokinin (CCK) on neurons of the neostriatum was studied in rats anaesthetized with urethane. The most frequently observed effect of the sulphated octapeptide (CCK-8S) on striatal neurons was excitation. Spontaneously active neurons responded more often to CCK-8S than quiescent cells. Silent, primarily non-responsive neurons could often be stimulated with CCK-8S using glutamate to induce an ongoing discharge. Thus, 45.8% of the 177 neurons studied changed their discharge rate by more than 30%. Certain CCK receptor antagonists could prevent the effect of CCK-8S, fully or at least partly, in the majority of CCK-responsive neurons. The data suggest that cholecystokinin modulates the firing of active neostriatal neurons via the CCKA or the CCKB receptor type. Furthermore, we compared neuronal responses to glutamate with those recorded during concomitant administration of CCK-8S in order to study the interaction of both transmitters, which may be colocalized in striatal afferents. CCK-8S mainly enhanced the excitatory effect of glutamate on striatal neurons, but in several neurons the response to glutamate was reduced. The CCKB receptor antagonist could prevent CCK-8S from increasing the glutamate-induced activation.

Characterization of somatostatin‐ and cholecystokinin‐immunoreactive periglomerular cells in the rat olfactory bulb

“…We cannot discard a similar action for CCK in the glomerular circuits, insofar as the distribution of the GABAergic PG matches well with the distribution of the CCK‐containing PG in both the sensory and the synaptic subcompartments of the glomerular neuropil. Finally, CCK might exert a direct excitatory effect upon its targets, as has been reported for the striatum (Davidowa et al, 1995, 1997; Wu and Wang, 1996), hippocampus (Gronier and Debonnel, 1995), and thalamus (Cox et al, 1995). The synaptic targets of the CCK‐containing PG are the mitral and tufted cells, but, in that this peptide is released extrasynaptically, the putative targets of the action of the CCK could be any other element taking part in the glomerular circuitry and expressing CCK receptors.…”

Cholecystokinin activates both A- and C-type vagal afferent neurons

“…The majority of electrophysiological studies have found that CCK depolarizes neurons in the peripheral nervous system (35,38,51), spinal cord (48), and brain (8,10,14,57,71,72). However, hyperpolarizing responses have also been observed in some neurons (8,38,73), and one study found that CCK augments the hyperpolarizing effects of dopamine in the ventral mesencephalon (10).…”

CCK as a modulator of cardiovascular function

“…Its localisation in synaptic vesicles and release by calcium dependent mechanisms (Emson et al, 1980), together with the excitatory effects on neurones in many brain areas (e.g. Brack and Lovick, 2007;Davidowa et al, 1995;Munro et al, 1998) suggest that it functions as a neurotransmitter. CCK-8 binding sites are widely distributed throughout the rat brain, with an especially high concentration in the forebrain (Van Dijk et al, 1984).…”