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.