Influence of Thiamine on the Behavioral Sensitivity to Ethanol

Changes in sensitivity to ethanol's rate‐decreasing effects on operant performance were examined in control rats and cohorts that received diet‐induced or diet + pyrithiamine‐induced thiamine deficiency. Seven groups of male Sprague‐Dawley rats (12 rats/group) were trained in a 5‐cycle lever‐press operant task under a fixed‐ratio 30 schedule of food reinforcement. Once trained to maintain consistent operant performance across all 5 cycles, each rat was tested with various doses of ethanol injected at the beginning of each timeout cycle. Each group of rats demonstrated equivalent saline baseline operant performance and ED 50 for ethanol's rate‐suppressing effects. Training sessions were suspended and rats received either a short‐ (9 days) or long‐term (5‐week) exposure to regular rat chow diet or thiamine‐deficient diet, and received either saline or pyrithia‐mine injections in a 2 × 2 design. Three additional control groups were maintained on a regular rat chow diet and received supplemental injections of either thiamine + pyrithiamine injections, thiamine + saline injections, or saline + pyrithiamine injections. The controlled diet phase continued until the development of overt signs of thiamine deficiency, at which time thiamine supplements were administered for 4 days. In phase 3, all rats were retrained in the operant task and a second ethanol dose‐effect function was generated. A history of thiamine deficiency and recovery failed to shift the behavioral dose‐effect functions significantly for ethanol and their associated blood alcohol curves. Most interestingly, significant behavioral sensitization to ethanol's rate suppressant effects was demonstrated in the two control groups of rats receiving regular rat chow diet in combination with supplemental injections of thiamine and either saline or pyrithiamine. The control group receiving regular rat chow diet and twice daily injections of saline and pyrithiamine failed to demonstrate overt signs of thiamine deficiency or significant shifts in the behavioral dose‐effect functions. We suggest a possible interaction between a surfeit of extracellular thiamine levels, and a subsequent decrease in magnesium levels may be involved in the development of increases in ethanol sensitivity.