Interactive effects of cholecystokinin-8S and various serotonin receptor agonists on the firing activity of neostriatal neuronesin rats.

In rats anaesthetized with urethane single unit activity was extracellularly recorded in the neostriatum, and several drugs were microiontophoretically ejected. Separate administration of the sulfated octapeptide cholecystokinin (CCK-8S), serotonin (5-HT) or 8-OH-DPAT (a 5-HT(1A/7) receptor agonist) predominantly induced increases in the neuronal discharge rates (Wilcoxon test significant P<0.05), whereas the 5-HT(2A/2C) receptor agonist DOI affected only a few neurones and mainly reduced firing. After coadministration of CCK-8S and serotonin, activating effects also predominated (Wt P<0.05), but the neuronal responsiveness was significantly reduced (Chi2P<0.01). Similarly, concomitant application of CCK-8S and 8-OH-DPAT led to significant activation accompanied with a reduction of inhibitory effects. The block of serotonin- or 8-OH-DPAT-effects through specific 5-HT(1A) receptor antagonists implies the involvement of this receptor subtype within the striatum. In conclusion, concomitant action of CCK-8S and serotonin induces a mean level of neuronal activation that might promote normal function.

Cholinergic modulation of neuronal responses to cholecystokinin in anesthetized rats.

The aim of this study was to investigate whether the effects of the neuropeptide cholecystokinin on neuronal firing can be changed by acetylcholine in various structures of the brain. Single unit activity was extracellularly recorded in rats anesthetized with urethane. The neurons were located in several nuclei of the thalamus, the basal ganglia and the cerebral cortex. Neurons responding to the sulfated octapeptide of cholecystokinin (CCK-8S) were mainly activated by the drug [Wilcoxon test (Wt) p < 0.0001, n=113]. Thalamic neurons could also increase the number of burst discharges (Wt p < 0.005, n=39). Iontophoretically administered acetylcholine could reduce the activating effects of CCK-8S on firing and burst discharges. In its presence, even inhibitory effects of CCK-8S predominated (Wt p < 0.0001, n=113). The suppressive action seemed not to depend on the direction of the effect of acetylcholine itself and concerned neurons of all locations studied. Atropine could diminish or block the suppressive action of acetylcholine. In the presence of both drugs, CCK-8S mainly activated the neurons (Wt p < 0.005, n=43). Atropine itself did not significantly change the responses to CCK-8S (Wt p > 0.05). It can be concluded that cholecystokinin may reduce neuronal firing instead of increasing it during activation of the cholinergic system.

Effects of cholecystokinin agonists on striatal neurons are reduced by acetylcholine.

The present study investigated whether acetylcholine, a transmitter of striatal interneurons, modulates responses of neostriatal neurons to agonists of the neuropeptide cholecystokinin (CCK). Single unit activity was recorded in rats anesthetized with urethane. Acetylcholine and CCK agonists (the CCKA receptor agonists A-71378 and A-71623; the CCKB receptor agonist Suc-CCK-4) were iontophoretically administered alone and in combination. The CCK agonists excited about one third of the neurons. The excitatory effects of both the CCKB and the CCKA receptor agonists were mainly reduced or changed to suppression of activity by acetylcholine (Wilcoxon test p < 0.001). Atropine did not significantly change the neuronal responses to the CCK agonists. The suppressive action of acetylcholine could be diminished by additional administration of atropine. The results suggest that the modulatory action of cholecystokinin does not only depend on the actual state of excitability in striatal neurons, but could be changed by acetylcholine released from interneurons.