Variants of contextual fear conditioning are differentially impaired in the juvenile rat by binge ethanol exposure on postnatal days 4-9

Abstract

Neonatal ethanol exposure in the rat is known to partially damage the hippocampus, but such exposure causes only modest or inconsistent deficits on hippocampus-dependent behavioral tasks. This may reflect variable sensitivity of these tasks or residual function following partial hippocampal injury. The context preexposure facilitation effect (CPFE) is a variant of context conditioning in which context exposure and immediate shock occur on successive occasions. During testing, preexposed rats freeze more than non-preexposed controls. The CPFE is more sensitive to anterograde hippocampal injury than standard contextual fear conditioning (e.g., Rudy JW, O'Reilly RC. Conjunctive representations, the hippocampus, and contextual fear conditioning. Cogn Affect Behav Neurosci 2001;1:66-82). We report that rats exposed to a high binge dose of ethanol (5.25g/kg/day) over postnatal days [PD] 4-9 failed to demonstrate the CPFE when preexposed to the conditioning context on PD31, relative to sham-intubated and undisturbed controls (Experiment 1). Neonatal alcohol disrupted conditioned freezing to a much lesser extent relative to controls when context preexposure was followed by a standard context conditioning trial rather than immediate shock (Experiment 2). Fear conditioning to a discrete auditory cue (tone) was unaffected by neonatal alcohol exposure ruling out possible performance effects (Experiment 3). These findings suggest that the CPFE is an especially sensitive task for detecting hippocampal injury produced by neonatal alcohol. Mixed results with other tasks may reflect residual hippocampal function and/or the use of alternate neurobehavioral systems or "strategies" following alcohol-induced brain damage.

Fig. 1

Mean (± SE) percent freezing during the 5 minute test of fear conditioning in Experiment 1. Dosing conditions include Group UD (undisturbed), Group SI (sham-intubated), and Group EtOH (5.25 g/kg/day). Rats from each group were preexposed to Context A (Pre, filled bars) or Context B (No Pre, clear bars). All rats were given an immediate shock 24h later in Context A, followed 24h after that with a test of freezing in Context A. Preexposure to Context A facilitated freezing during the test in Groups UD and SI. Neonatal ethanol treatment (PD4-9) disrupted this context preexposure facilitation effect. Group EtOH showed low levels of freezing in Context A regardless of preexposure condition (Pre vs. No Pre).

Fig. 2

Mean (± SE) percent freezing during the 5 minute test of fear conditioning that occurred 24h after Immediate-shock training in Experiment 2. Group and Treatment designations were as described in the Figure 1 caption. The context preexposure facilitation effect appeared in Groups UD and SI but not in Group EtOH.

Fig. 3

Mean (± SE) percent freezing during the 5 minute test of fear conditioning that occurred 24h after 120s-shock training in Experiment 2.. Dosing conditions were Group UD (undisturbed), Group SI (sham-intubated), and Group EtOH (5.25 g/kg/day). Rats from each group were preexposed to Context A (Pre, filled bars) or Context B (No Pre, clear bars). Twenty-four hours later, all rats were given shock 120s after placement into Context A, followed 24h after that with a 5-min test of freezing in Context A. Main effects of dosing condition and preexposure indicated that Group EtOH showed reduced levels of freezing relative to the other groups and preexposure facilitated conditioning in all groups.

Fig. 4

Percent freezing (mean ± SE) during 5 minute testing period with 5 10s presentations of a discrete auditory (tone) conditioned fear stimulus. Group UD (undisturbed), Group SI (sham-intubated), and Group EtOH (5.25 g/kg/day) did not differ significantly in CS-elicited freezing.