The Effects of Acute Cocaine and Cocaine Withdrawal on Rats' Short-Term Memory Performance During Delayed Match to Sample Tasks in Y-Maze and Two-Lever Operant Paradigm

Abstract

While an extensive literature exists on the effects of cocaine on many different behaviors, there has been little research on the effects of cocaine withdrawal in rats. Recently we have been developing delayed match to sample tasks (DMTS) in a Y-Maze paradigm and two-lever operant task pursuant to examining the effects of cocaine withdrawal on short term memory (STM). The absence of an observing response made the Y-maze task difficult to learn for many of the rats, and performance was highly variable. Nonetheless, rats that were able to master the task, showed a marginally significant decrease in STM performance during a week following 7 days of exposure to 45 mg/kg of cocaine per day over three hours compared to saline control conditions. Using a two lever DMTS task, we found consistently faster learning and less variability in performance with memory delays ranging from 3 to 8-sec. Using four pilot rats, we found a weak, transient decrease in DMTS performance compared to saline control conditions, during a week where 45 mg/kg of cocaine was administered after each daily training session, and after complete withdrawal from cocaine. Subsequently, we found that acute cocaine injections at 15 and 10 but not 5 mg/kg, prior to training sessions, disrupted DMTS performance. Although the two-lever DMTS task generates more accurate and less variable performance, it is more difficult to disrupt STM. Accordingly, we are modifying the training conditions to make STM more difficult, and therefore more sensitive to disruption.