Drug discrimination in rats: effects of mixtures of ditran and cholinesterase inhibitors

Abstract

Groups of rats were trained in a T-shaped maze to discriminate the effects produced by IP injections of ditran (1.60 mg/kg), either when given singly, or when combined with the acetylcholinesterase inhibitors neostigmine (0.25 mg/kg) or physostigmine (0.50 and 1.00 mg/kg), from the nondrug condition (saline). The results from this state-dependency (StD) model indicated that acquisition of the drug discrimination was similar for the 4 groups of rats. After drug discrimination was established the rats were tested with various drug combinations. Physostigmine (0.50 and 1.00 mg/kg) challenge reversed drug discrimination among rats trained with ditran solely or the ditran plus neostigmine combination. There was no antagonism among the ditran plus physostigmine trained rats. Involvement of the C.N.S. is implicated since tests with neostigmine did not upset ditran discrimination. In addition, survival rate of physostigmine treated mice is increased with ditran. In conclusion, this study indicates the usefulness of employing both training and transfer test procedures when evaluating antagonism in this StD model.