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

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.

Figure 1.

The mean (±SEM) discrimination ratio from the sample and choice phases of object recognition following post-sample injections of 0 (n = 23), 5 (n = 23), 10 (n = 23), and 20 (n = 23) mg/kg cocaine in Experiment 1. The * denotes a significant difference compared to 0 mg/kg cocaine choice phase discrimination ratio. The # denotes a significant difference when compared to the sample phase discrimination ratio.

Figure 2.

Experiment 2. (A) Mean (±SEM) distance moved in compartments paired (1–5) with injections of Vehicle (in CS−; n = 48) and 20 (in CS+; n = 48) mg/kg cocaine. The ** denotes a significant difference compared to CS− distance moved at all time points. (B) The mean (±SEM) distance moved during the 30 min test of conditioned locomotion in the compartment previously paired with Vehicle (CS−) and 20 mg/kg (CS+) (n = 48) cocaine. The @ denotes a significant difference compared to CS− distance moved. (C) The mean (±SEM) discrimination ratio produced during the sample and choice phase of object recognition following exposure to CS compartments previously paired with Vehicle (CS−) and 20 mg/kg (CS+) (n = 12) cocaine post-sample. The * denotes a significant difference compared to CS− choice phase discrimination ratio. The # denotes a significant difference compared to sample phase discrimination ratio.

Figure 3.

The mean (±SEM) discrimination ratio from the sample and choice phases of object recognition following post-sample injections of 0 (n = 23), 0.1 (n = 23), 0.2 (n = 23), and 0.4 (n = 23) mg/kg nicotine in Experiment 3. The * denotes a significant difference compared to 0 mg/kg nicotine choice phase discrimination ratio. The # denotes a significant difference compared to sample discrimination ratio.

Figure 4.

Experiment 4. (A) Mean (±SEM) distance moved during pairings (1–5) of locomotion to compartments paired with injections of vehicle (in CS−; n = 48) and 0.4 (in CS+; n = 48) mg/kg nicotine after 30 min. The * denotes a significant difference compared to Vehicle CS−. The & denotes a significant difference compared to 0.4 mg/kg in CS+ nicotine pairing 5. (B) The mean (±SEM) distance moved during the 30 min test of conditioned locomotion in compartments previously paired with Vehicle (n = 48) (CS−) and 0.4 (n = 48) mg/kg (CS+) nicotine. The * denotes a significant difference compared to CS− distance moved. (C) The mean (±SEM) discrimination ratio calculated during the sample and choice phases of object recognition following exposure to a compartment previously paired with Vehicle (n = 12) (CS−) and 0.4 (n = 12) mg/kg (CS+) nicotine post-sample. The * denotes a significant difference compared to CS− choice phase discrimination ratio. The # denotes a significant difference compared to sample discrimination ratio.

Figure 5.

Experiment 5. (A) The mean (±SEM) discrimination ratio produced during the sample and choice phases of object recognition in response to an injection of 0 (n = 12) and 20 (n = 12) mg/kg cocaine 6 h post-sample. (B) The mean (±SEM) discrimination ratio produced during the sample and choice phases of object recognition in response to exposure to a compartment previously paired with 0 (n = 12) (CS−) and 20 mg/kg (n = 12) (CS+) cocaine 6 h post-sample. (C) The mean (±SEM) discrimination ratio produced during the sample and choice phase of object recognition in response to an injection of 0 (n = 12) and 0.4 (n = 12) mg/kg nicotine 6 h post-sample. (D) The mean (±SEM) discrimination ratio produced during the sample and choice phase of object recognition in response to exposure to a compartment previously paired with 0 (n = 12) (CS−) and 0.4 (n = 12) mg/kg (CS+) nicotine 6 h post-sample. There was no evidence of object recognition in any condition when the drug or CS+ exposure was delay by 6 h.

Figure 6.

(A) Mean (±SEM) distance moved during pairings (1–5) of locomotion to compartments paired with injections of vehicle (n = 11) and 0.4 (n = 11) mg/kg nicotine after 30 min. The * denotes a significant difference compared to 0 mg/kg in CS−. (B) The mean (±SEM) time spent in a vehicle-paired (n = 11) and 0.4 mg/kg nicotine-paired (n = 11) chamber during the habituation and test of conditioned place preference. The * denotes a significant difference compared to the vehicle-paired chamber.