Improving unbiased left/right training of rats and use of physostigmine to counteract scopolamine-induced short-term memory impairment

Abstract

Rationale: The DNMTP task measures short-term / working memory uncontaminated by learning capacity,  spatial abilities, motor performance or general motivational and arousal factors. However, DNMTP training  of rats can take two months, and we aimed to reduce this. Methods: Two experiments were conducted on rats  in an operant DNMTP task. Improvements were made on the training procedure. The method was validated  by replicating the effect of scopolamine on working memory. The experiments also explored the influence  of physostigmine in reversing impairment induced by scopolamine. Thus in experiment 1, ten Lewis rats  were trained in an operant DNMTP task (1, 2, 4 and 8 s delay intervals) before 9 of them received vehicle,  scopolamine, saline or combinations of scopolamine and physostigmine. In experiment 2, ten Lewis rats (5  old and 5 young) were trained in the same task (1, 2, 4, 8 and 16 s delay intervals). There were six treatments:  0.05 mg/kg scopolamine, 0.1 mg/kg physostigmine or 0.15 mg/kg physostigmine, control involving  saline or involving no injection and no handling, and finally a combined treatment of 0.05mg/kg scopolamine  and 0.15 mg/kg physostigmine. In both experiments scopolamine significantly reduced correct  responses, nose-pokes and lever presses compaired to control conditions. Furthermore, in experiment 2,  there was insignificant difference between saline and combined scopolamine/physostigmine for correct  responses and for delay prior to pressing the sample lever. As expected, there was significant difference  between scopolamine and combined scopolamine/physostigmine for correct responses, for delay prior to  pressing the sample lever and for delay prior to pressing the non-matching lever. As a result, the animals  were ready for drug injection after 17 days from habituation and the method ensured that there were no dropouts  due to left or right lever preference. This is a shorter training period than previously thought necessary.  The brief training method was validated by replicating the effect of scopolamine on working memory.