Learning deficits in aged rats pretreated chronically with barbital and tested late in abstinence: alleviation by tetrahydroaminoacridine.

Physostigmine and tetrahydroaminoacridine (THA) have been reported to improve cognitive function in patients with Alzheimer's disease. Two experiments were conducted to examine the effects of these anticholinesterase agents on learning in aged rats pretreated chronically with barbital. In the first experiment animals received barbital in their drinking water for 46 weeks. Controls were given only water. On days 100-104 of abstinence, when the animals were 20 months old, acquisition of the Morris maze task was initiated after treatment with physostigmine. It was found that physostigmine improved learning of the maze task in control but not barbital treated rats. In the second experiment animals received barbital solution or water as in experiment one. On days 100-103 of abstinence they were injected with THA before being tested in the Morris water maze. It was found that THA improved learning in both barbital treated and control rats. These results corroborate clinical findings of improved cognitive function following treatment with THA, and suggest that the therapeutic effects of THA may be mediated by mechanisms distinct from cholinesterase inhibition. Furthermore chronic barbital treatment could be used as a model to study cognitive disturbances in experimental animals.