Reversibility of object recognition but not spatial memory impairment following binge-like alcohol exposure in rats

Abstract

Excessive alcohol use leads to neurodegeneration in several brain structures including the hippocampal dentate gyrus and the entorhinal cortex. Cognitive deficits that result are among the most insidious and debilitating consequences of alcoholism. The object exploration task (OET) provides a sensitive measurement of spatial memory impairment induced by hippocampal and cortical damage. In this study, we examine whether the observed neurotoxicity produced by a 4-day binge ethanol treatment results in long-term memory impairment by observing the time course of reactions to spatial change (object configuration) and non-spatial change (object recognition). Wistar rats were assessed for their abilities to detect spatial configuration in the OET at 1 week and 10 weeks following the ethanol treatment, in which ethanol groups received 9-15 g/kg/day and achieved blood alcohol levels over 300 mg/dl. At 1 week, results indicated that the binge alcohol treatment produced impairment in both spatial memory and non-spatial object recognition performance. Unlike the controls, ethanol treated rats did not increase the duration or number of contacts with the displaced object in the spatial memory task, nor did they increase the duration of contacts with the novel object in the object recognition task. After 10 weeks, spatial memory remained impaired in the ethanol treated rats but object recognition ability was recovered. Our data suggest that episodes of binge-like alcohol exposure result in long-term and possibly permanent impairments in memory for the configuration of objects during exploration, whereas the ability to detect non-spatial changes is only temporarily affected.

Figure 1

Schematic representation of the object exploration task and geometric arrangement of objects. S1, familiarization session (absence of objects); S2–S7, habituation sessions (open circle: object1; open square: object2); S8–S9, spatial change sessions (open circle: object1; open square: object2); S10, non-spatial change session (open triangle: object3; open square: object2).

Figure 2

Binge alcohol-induced neurotoxicity in the hippocampal dentate gyrus (DG) and the entorhinal cortex (EC). Sections were stained by Fluoro-Jade B (FJB) to visualize neurodegeneration. Panels (A), (B), (C), and (D) show representative sections visualizing labeled neurons in both the DG, (A) and (B), and the EC, (C) and (D) of animals without (A) and (C) or with ethanol exposure (B) and (D). Panel (E) shows quantitation of the histological data demonstrating alcohol-induced neurodegeneration (*p<0.05, difference from control group). No neurodegeneration was found in animals exposed to the non-alcohol solution. Data are given as the mean number of FJB positive cells/mm²±SEM; solid bars: control animals not exposed to alcohol; open bars: alcohol treated animals. For detailed statistics, see Results.

Figure 3

Binge alcohol treatment does not alter locomotor activity throughout the 10 sessions (S1–S10) of the object exploration task. Alcohol exposed (EtOH, open circle) and non-exposed (Control, solid circle) animals showed similar habituation to the task following 1 week (A) and 10 weeks (B) from the exposure. Data are given as the mean distance traveled expressed in cm ± SEM. For detailed statistics, see Results.

Figure 4

Binge-like ethanol exposure impaired the ability to detect the spatial change 1 week following the binge alcohol treatment. When object 2 (obj. 2) was displaced to a new location, non-exposed rats (Control) more than doubled the number of contacts (A) as well as the duration of contacts (B) with the object from session 7 (S7, white bars) to session 8 (S8, black bars) whereas both measures were unaltered in alcohol exposed (EtOH) rats. Number (C) and duration (D) of contacts with the non-displaced object, object1 (obj.1), did not change between S7 and S8 in either group. Values are given as the mean (±SEM) number and duration of contacts with both the displaced and non-displaced object. **p<0.01, ***p<0.001, difference from Control performance in S7; #p<0.05, difference from Control performance in S7. For detailed statistics, see Results.

Figure 5

Binge-like ethanol exposure impaired the ability to detect the spatial change 10 weeks following the binge alcohol treatment. When object 2 (obj.2) was displaced to a new location, non-exposed rats (Control) greatly increased the number of contacts (A) as well as the duration of contacts (B) with obj. 2 from session 7 (S7, white bars) to session 8 (S8, black bars) whereas both measures were unaltered in alcohol exposed (EtOH) rats. Number (C) and duration (D) of contacts with the non displaced object, object1 (obj.1), did not change between S7 and S8 in either group. Values are given as the mean (±SEM) number and duration of contacts at both the displaced and non-displaced object. *p<0.05, **p<0.01, difference from Control performance in S7; #p<0.05, difference from Control performance in S7. For detailed statistics, see Results.

Figure 6

Binge-like ethanol exposure impaired the ability to detect the non-spatial change at 1 week (A) but not 10 weeks (B) following the alcohol treatment. (A) When a novel object, object 3, replaced object 1, non-exposed rats (Control) greatly increased the duration of contacts with the novel object compared with the old one from session 9 (S9, white bars) to session 10 (S10, black bars), whereas duration of contacts was unaltered in alcohol exposed (EtOH) rats. (B) Both Control and EtOH groups detected the non-spatial change as shown by the increased duration of contacts with the novel object in S10 vs. S9. Values are given as the mean (±SEM) duration of contacts (expressed in seconds) with the novel object. *p<0.05, difference from Control performance in S9; **p<0.01, difference from EtOH performance in S9. For detailed statistics, see Results.