Cocaine, nicotine, and their conditioned contexts enhance consolidation of object memory in rats.

Michael Wolter,Talia Speigel,Ethan Huff,Francesco Leri,Boyer D Winters

doi:10.1101/lm.048579.118

Abstract

To test the hypothesis that drugs of abuse and their conditioned stimuli (CSs) enhance memory consolidation, the effects of post-training exposure to cocaine and nicotine were compared to the effects of post-training exposure to contextual stimuli that were paired with the effects of these drugs. Using the object recognition (OR) task, it was first demonstrated that both 10 and 20 mg/kg cocaine, and 0.2 and 0.4 mg/kg nicotine, enhanced recognition memory when administered immediately after, but not 6 h after the sample phase. To establish the drug CSs, rats were confined for 2 h in a chamber (the CS+) after injections of 20 mg/kg cocaine, or 0.4 mg/kg nicotine, and in another chamber (the CS−) after injections of vehicle. This was repeated over 10 d (5 drug/CS+ and 5 vehicle/CS− pairings in total). At the end of this conditioning period, when tested in a drug-free state, rats displayed conditioned hyperactivity in the CS+ relative to the CS−. More important, immediate, but not delayed, post-sample exposure to the cocaine CS+, or nicotine CS+, enhanced OR memory. Therefore, this study reports for the first time that contextual stimuli paired with cocaine and nicotine, like the drugs themselves, have the ability to enhance memory consolidation.

Highlights

Thorndike (1911) proposed that a reinforcer acts as an event that “stamps-in” the association between stimuli and responses
The analysis of total object exploration was nonsignificant for the sample and choice phases
When cocaine injections were delayed by 6 h, there was no evidence of object memory, as the sample and choice phase discrimination ratios did not differ (Fig. 5A)

Summary

Introduction

Thorndike (1911) proposed that a reinforcer acts as an event that “stamps-in” the association between stimuli and responses This idea has been formalized by the hypothesis that reinforcers exert their behavioral effects by enhancing memory consolidation: a time-dependent process in which a memory trace becomes stabilized and less sensitive to interference (White and Milner 1992; McGaugh and Roozendaal 2009). The experimental approach used to explore the memory enhancing function of reinforcers involves manipulations delivered immediately, or soon after, training on a given task (White 1996; Rkieh et al 2014) This is a key experimental requirement because it is believed that a memory trace is labile, and sensitive to modulations, during a critical period of minutes to hours that follow the experience of learning (McGaugh 2000). Cocaine and nicotine were selected because they have been found previously to enhance memory consolidation (Introini-Collison and McGaugh 1989; Beer et al 2013) and because they support classical conditioning of various responses (Jackson et al 2009; Johnson et al 2012)

Methods

Results

Conclusion