Different modulation of cholinergic neuronal systems by dynorphin A (1-13) in carbon monoxide-exposed mice

The effects of dynorphin A (1-13), a kappa-opioid receptor agonist, on the content of acetylcholine (ACh) and high K+-induced release of endogenous ACh were studied in mice exposed to carbon monoxide (CO). Mice were exposed to CO 3 times at 1-hr intervals and used 7 days after CO exposure. Administration of dynorphin A (1-13) (1.5 and 5.0 nmol/mouse, intracerebroventricularly) 15 min before killing significantly increased the ACh content in the striatum and hippocampus of control mice, but had no effect on the ACh content in CO-exposed mice. Dynorphin A (1-13) did not change the choline acetyltransferase (EC 2.3.1.6) activity in control or CO-exposed mice. The high K+-induced endogenous ACh release from hippocampal slices in CO-exposed mice was significantly lower than that of controls, although exposure to CO did not affect the basal release of endogenous ACh from hippocampal slices compared with controls. Dynorphin A (1-13) caused dose-dependent decreases in high K+-induced release of endogenous ACh from hippocampal slices in control mice. This inhibitory effect of dynorphin A (1-13) was blocked by co-perfusion with nor-binaltorphimine, a selective K-opioid receptor antagonist. On the other hand, dynorphin A (1-13) did not decrease high K+-induced release of endogenous ACh from hippocampal slices in CO-exposed mice. These results suggest that dysfunction of the cholinergic system occurred after exposure to CO, and as a result the inhibitory effects of dynorphin A (1-13) may be blocked in CO-exposed mice.