Thiamine deficiency depletes cortical norepinephrine and impairs learning processes in the rat

Several lines of evidence indicate that thiamine deficiency causes the Wernicke-Korsakoff syndrome, a human memory disorder. The present study examined behavioral deficits in rats after recovery from a bout of thiamine deficiency. Following behavioral testing, the brains were dissected into regions and assayed biochemically for levels of dopamine, norepinephrine, serotonin and the primary metabolites of these monoamines. Based on previous findings in this laboratory, we predicted that thiamine deficiency not only produces behavioral deficits but loss in catecholamines as well. Impairments were observed for a spatial delayed alternation task that had been learned prior to experimental treatment. In addition, experimental animals were impaired in their ability to acquire two novel tasks, active and passive shock avoidance, after recovery from the acute effects of thiamine deficiency. Comparable deficits were not observed for a number of reflex responses that were measured to assess the general neurological state of the animals. Biochemical analyses revealed that the concentration of norepinephrine was reduced significantly in cortex-hippocampus and olfactory bulb but not in other regions, while dopamine and serotonin levels were not altered in any brain region examined. These data demonstrate that a bout of thiamine deficiency can produce persistent deficits in brain norepinephrine and concomitant decrements in behavioral measures of learning and memory. These results are consistent with our hypothesis and evidence that noradrenergic deficits contribute to the amnesic symptoms of Korsakoff's psychosis.