Combined administration of MK-801 and cycloheximide produces a delayed potentiation of fear discrimination memory extinction

Abstract

Mixed evidence exists regarding the role of N-methyl-D-aspartate (NMDA) receptors in memory reconsolidation. We provide no evidence that NMDA receptors are involved with memory reconsolidation, but instead demonstrate that prereactivation systemic MK-801 injection, combined with postreactivation intrabasolateral amygdala (BLA) cycloheximide infusion, produces a delayed potentiation of extinction learning. These data suggest that an interaction between NMDA antagonism and protein synthesis inhibition may enhance extinction by exerting effects outside of the intended reconsolidation manipulation window. The present work demonstrates a novel pharmacological enhancement of extinction, and underscores the importance of employing proper control procedures in reconsolidation research. (PsycINFO Database Record

Figure 1

(A) Experiment timeline. (B) Cannula placement for all animals included in analysis (atlas images modified from The Rat Brain in Stereotaxic Coordinates (3^rd ed.), Bregma −2.56mm and Bregma −3.14mm, by G. Paxinos & C. Watson, 1997, San Diego, CA: Academic Press, Inc with permission from Elsevier). The number of animals in each group was as follows veh/veh = 6, veh/cyclo = 10, MK-801/veh = 9, MK-801/cyclo = 8; N = 33. (C–F) The percentage of time spent freezing during each training session (C), the reactivation session (D), each extinction session (E), and the CTX− test (F). Bars represent ± 1 SEM.

Figure 2

(A) Experiment timeline. (B) Cannula placement for all animals included in analysis (atlas images modified from The Rat Brain in Stereotaxic Coordinates (3^rd ed.), Bregma −2.56mm and Bregma −3.14mm, by G. Paxinos & C. Watson, 1997, San Diego, CA: Academic Press, Inc with permission from Elsevier). The number of animals in each group was as follows: veh/veh = 7, MK-801/cyclo = 8, no surgery = 10; N = 25. (C–E) The percentage of time spent freezing during each training session (C), each extinction session (D), and retraining (E). Bars represent ± 1 SEM.