Post-training, but not post-reactivation, administration of amphetamine and anisomycin modulates Pavlovian conditioned approach

Abstract

The psychostimulant, amphetamine (AMPH), and the protein synthesis inhibitor, anisomycin (ANI), have been shown to modulate the consolidation and reconsolidation of several types of learning. To determine whether Pavlovian conditioned approach (PCA) is modulated in a similar manner, we examined the effects of post-training and post-reactivation administration of both AMPH and ANI on memory for PCA. Male Long-Evans rats received PCA training sessions during which presentations of a CS+ were followed by sucrose delivery. AMPH (1 mg/kg, s.c.) injected immediately but not 6h after the first training session enhanced PCA behavior. ANI (150 mg/kg, s.c.) injected immediately but not 3h after the first training session impaired PCA behavior. This impairment was not due to the development of a conditioned taste aversion. To examine whether PCA can also be modulated by post-reactivation administration of AMPH and ANI, rats were given an injection of AMPH, ANI, or vehicle immediately after a memory reactivation session. Upon testing, the behavior of both the AMPH- and the ANI-treated rats was unaffected. This result remained consistent when the experiment was repeated with changes to various behavioral parameters (i.e., amount of training, length of memory reactivation). These findings indicate that AMPH and ANI act during the post-training but not the post-reactivation period to enhance and impair, respectively, the learning of PCA. This suggests that the consolidation of PCA can be modulated in a manner comparable to other types of learned associations, but once learned, the memory appears to be relatively robust and stable.

Figure 1. Effect of post-training injections of amphetamine on PCA behavior

a) Experimental design b) PCA behavior during the training sessions expressed as a mean difference score (the number of port entries during the CS+ minus the number of port entries during the CS−) ± SEM (vehicle, n=15; AMPH – imm, n=12; AMPH – 3 hrs, n=7). c) PCA behavior during Training Session 2 expressed as a mean difference score ± SEM (vehicle, n=15; AMPH – imm, n=12; AMPH – 3 hrs, n=7). The data from the session is separated into 3 bins that each consist of 5 individual trials. *P<.05

Figure 2. Effect of delayed post-training injections of amphetamine on PCA behavior

a) Experimental design b) PCA behavior during the training sessions expressed as a mean difference score ± SEM (vehicle, n=7; AMPH – 6 hrs, n=8). c) PCA behavior during Training Session 2 expressed as a mean difference score ± SEM (vehicle, n=7; AMPH – 6 hrs, n=8). The data from the session is separated into 3 bins that each consist of 5 individual trials.

Figure 3. Effect of post-training injections of anisomycin on PCA behavior

a) Experimental design b) PCA behavior during the training sessions expressed as a mean difference score ± SEM (vehicle, n=15; ANI – imm, n=7; ANI – 3 hrs, n=7). **P<.01 c) Experimental design using a lower dose of anisomycin d) PCA behavior during the training sessions expressed as a mean difference score ± SEM (vehicle, n=8; ANI, n=8).

Figure 4. Effect of post-training injections of anisomycin on sucrose preference

a) Experimental Design b) Sucrose preference expressed as a mean sucrose preference ratio (the volume of sucrose consumed divided by total volume of liquid consumed) ± SEM. (vehicle, n=8; ANI, n=8) c) PCA behavior during the training sessions expressed as a mean difference score ± SEM (vehicle, n=8; ANI, n=8). *P<.05

Figure 5. Effect of post-reactivation injections of anisomycin on PCA behavior

a) Experimental Design b) Effect of post-reactivation injections of anisomycin when the initial training consists of 2 sessions. PCA behavior during the reactivation and test sessions is expressed as a mean difference score ± SEM. (vehicle, n=19; ANI, n=20) c) Effect of post-reactivation injections of anisomycin when the initial training consists of 4 sessions. PCA behavior during the reactivation and test sessions is expressed as a mean difference score ± SEM. (vehicle, n=8; ANI, n=8) d) Effect of post-reactivation injections of anisomycin when the initial training consists of 7 sessions. PCA behavior during the reactivation and test sessions is expressed as a mean difference score ± SEM. (vehicle, n=8; ANI, n=8)

Figure 6. Effect of changes to the reactivation session on the ability of post-reactivation injections of anisomycin to affect PCA behavior

a) Experimental design b) Effect of post-reactivation injections of anisomycin when the reactivation session includes the delivery of sucrose. PCA behavior during the reactivation and test sessions is expressed as a mean difference score ± SEM. (vehicle, n=8; ANI, n=8) c) Effect of post-reactivation injections of anisomycin when the reactivation session is shortened to include only one presentation of each CS. PCA behavior during the reactivation and test sessions is expressed as a mean difference score ± SEM. (vehicle, n=8; ANI, n=8)

Figure 7. Effect of post-reactivation injections of amphetamine on PCA behavior

a) Experimental design b) Effect of post-reactivation injections of amphetamine when the initial training consists of 2 sessions. PCA behavior during the reactivation and test sessions is expressed as a mean difference score ± SEM. (vehicle, n=8; AMPH, n=8) c) Effect of post-reactivation injections of amphetamine when the initial training consists of 7 sessions. PCA behavior during the reactivation and test sessions is expressed as a mean difference score ± SEM. (vehicle, n=19; AMPH, n=20)