We have demonstrated a deficit in working memory and/or consolidation of information in working memory into reference memory by a single oral dose of the neurotoxin trimethyltin (TMT). Moreover, TMT causes loss of hippocampal corticosterone receptions and increases brain glial fibrillary acidic protein (GFAP), an index of the astryocytic reaction to diverse types of CNS lesions. We tried to block the TMT-induced cognitive deficit and biochemical markers by treating rats with purified mixed ganglioside (GS) for 21 days, starting 2 days before the TMT treatment. As expected, TMT decreased the number of corticosterone receptors in hippocampi and increased the GFAP concentration in hippocampi and to a lesser extent, in frontal cortices, measured more than 8 months after treatment. The small increase in GFAP in frontal cortices was attenuated by GS but not in hippocampi. The pronounced learning deficits caused by TMT were attenuated to a small extent by GS in the TMC-GS group, when a learning criterion was used for the last session's performance of acquired level-directed behavior. GS also delayed the appearance of significant performance differences between Controls and TMT-treated rats, when probed with a progressive fixed-ratio schedule of reinforcement. However, most measures of learning and performance indicated that GS did not block the dysfunctional consequences of TMT treatment but instead caused similar functional decrements in rats treated with water instead of TMT. (Copyright (c) 1992 by Intox Press, Inc.)