Abstract

Pyrithiamine-induced thiamine deficiency (PTD) in rats causes deficits on a wide variety of spatial-memory tasks. PTD-induced memory deficits are thought to result from damage in areas of the diencephalon that are selectively vulnerable to the metabolic disruption of thiamine deficiency. However, a high incidence of seizures during the late stages of PTD treatment complicates this interpretation, as these seizures may contribute to the neuropathological and behavioural outcome of PTD. The present experiment assessed spatial allocentric working-memory in recovered PTD rats. Two groups of rats received PTD treatment; one group received diazepam (5mg/kg) upon the first sign of overt seizures in order to attenuate them until treatment reversal (Group PTD+DZ), and the other group received no diazepam (Group PTD). Following recovery, the rats were trained on a delayed matching-to-place (DMTP) task in a water maze, and tested with retention delays of 4, 30, and 120 seconds. Both experimental groups displayed DMTP acquisition defecits, and PTD rats were subsequently impaired at all retention delays. By contrast, the PTD+DZ rats were impaired only at the 120-sec delay. Moreover, thalamic neuropathology was attenuated in the PTD+DZ rats. Although further studies will be needed to determine the mechanism by which diazepam exerts its protective effects in this model, the present study suggests that PTD-induced neuropathology and memory deficits can be attenuated by treatments that reduce seizure activity.