The context preexposure facilitation effect in mice: a dose-response analysis of pretraining scopolamine administration

Abstract

The context preexposure facilitation effect (CPFE) is an elaboration of contextual fear conditioning and refers to enhanced contextual conditioning resulting from preexposure to the context prior to a separate, brief context-shock episode. A version of the CPFE developed by Rudy and colleagues in rats has demonstrated greater sensitivity to pre-training hippocampal insult relative to standard contextual fear conditioning preparations. Our aim was to adapt the Rudy CPFE procedures to mice. In Experiment 1 we compared performance of young adult male C57BL6/J mice on two versions of the CPFE. One version - not previously used in mice - adapted methods established by Rudy and colleagues, and the other CPFE task replicated procedures previously established in this mouse strain by Gould and colleagues. In Experiment 2 we compared the effects of pre-training intraperitoneal administration of moderate levels of scopolamine or methylscopolamine on contextual conditioning between mice trained using the Rudy CPFE method and a separate group trained using standard contextual fear procedures. Scopolamine is a muscarinic cholinergic receptor antagonist that impairs hippocampal function. Robust freezing to the conditioning context was observed in mice trained using the Rudy CPFE method (Experiment 1), and greater scopolamine-induced impairments in contextual freezing were observed using this CPFE method relative to mice trained using standard contextual fear procedures (Experiment 2). These findings support use of the Rudy CPFE task as a behavioral assay for hippocampal function in mice.

Figure 1

Depiction of the experimental design used in Experiment 1. All phases of training are separated by 24 h. Black circles represent the black ice bucket used for transportation in ‘Rudy’ subjects and the open circles represent the clear polycarbonate cage used for transportation in ‘Gould’ subjects. Black triangles represent the experimental chamber (context) used for preexposure in experimental (Exp) subjects and during Phases 2 and 3 in all subjects. All sensory features of the environment (e.g., odor; tactile cues) are the same in conditions identified with a black triangle. In contrast, open triangles represent a context in which these sensory cues differ (used at Phase 4). Open squares represent the clear polycarbonate cage used for preexposure in Rudy and Gould control (Ctl) groups. ‘IM Shock’ refers to shock administration immediately following placement into the chamber at Phase 2 for Rudy groups. ‘Delay Shock’ refers to shock administration 5 sec following placement into the chamber at Phase 2 for Gould groups.

Figure 2

Mean percentage of freezing during each of the six minutes of the context test (Phase 3) for the four groups used in Experiment 1. Bars depict standard error of the mean.

Figure 3

Mean percentage of freezing as a function of training phase for the four groups used in Experiment 1. Bars depict standard error of the mean.

Figure 4

Mean percentage of freezing as a function of drug and dosage during Phases 1, 3, and 4 of training for subjects trained using Rudy CPFE procedures in Experiment 2. Bars depict standard error of the mean.

Figure 5

Mean percentage of freezing as a function of drug and dosage during Phases 1, 3, and 4 of training for subjects trained using standard fear conditioning procedures in Experiment 2. Bars depict standard error of the mean.