Do elevated dynorphins in fact contribute to cognitive dysfunction?
When rats were treated with high doses of ethanol, dynorphin content in the prefrontal cortex and hippocampus was increased a finding that was obviously similar to that obtained in human alcoholics. Importantly, ethanol treatment impaired animal behaviour in learning and memory tests. In next animal experiment a drug that selectively binds to the KOR receptor and blocks the effects of endogenous dynorphins, a KOR antagonist, was injected into ethanol-treated rats. Strikingly, this compound prevented the development of learning and memory deficits induced by alcohol. This indicates that upregulated dynorphins may play a crucial role in impairing learning and memory. Cycles of alcohol intoxication and withdrawal appear to stimulate the generation of dynorphins in the hippocampus and prefrontal cortex in rats as well as in human alcoholics. As a neurobiological feedback, elevated dynorphins may inhibit release of neurotransmitters such as glutamate and acetylcholine, which are essentially
