The DYN/KOR system has also been linked to ethanol-related cognitive impairment. One study conducted in Wistar rats found that six days of forced binge-like ethanol administration resulted in cognitive deficits (i.e., increased escape latency) in a water maze task and elevated DYN levels in the hippocampus (Kuzmin et al., 2013). Treatment with nor-BNI (either systemic or in the dorsal CA3 region of the hippocampus) restored escape behavior in the ethanol-exposed rats whereas systemic nor-BNI did not enhance performance in control subjects (Kuzmin et al., 2013). In accordance with these preclinical findings, a comparison of postmortem human brain tissue in alcoholic and control subjects revealed greater expression of prodynorphin and KOR mRNA in areas implicated in the cognitive control of addictive behavior — dorsolateral PFC, orbitofrontal cortex, and hippocampus (Bazov et al., 2013). Clearly, this is an area of therapeutic opportunity in which more research is needed.
