Research reportDifferent effects of scopolamine on the retrieval of spatial memory and fear memory
Introduction
Memory is considered to be a complex process that has multiple stages, including acquisition, consolidation, and retrieval. Compared to the numerous literatures about the mechanisms underlying the consolidation phase of memory [29], there are much fewer studies about the molecular requirements of memory retrieval [48]. Nevertheless, retrieval of memory is fundamental for our life as individuals [37].
Cholinergic system is known to be important for learning and memory [11], [23]. The participation of the cholinergic system in memory consolidation process has been extensively studied, but there are few data concerning the function of this system in memory retrieval process. Most studies have invested the influences of cholinergic function on the memory consolidation by post-training drug administrations [3], [5], [25], [38], [45], [47]. There are only a few papers concerning whether the cholinergic system plays a role in the memory retrieval. Barros et al. showed an enhanced effect on the retention performance in inhibitory avoidance task by intra-hippocampal pre-testing infusion of oxotremorine (a non-selective muscarinic agonist) and an amnestic effect of the non-selective muscarinic antagonist scopolamine [4]. That indicates the cholinergic muscarinic system in the hippocampus has a positive role in the memory retrieval process of the inhibitory avoidance task. In another study, however, intra-hippocampal pre-testing infusion of MT3 (2 μg/side, a selective muscarinic receptor subtype 4 antagonist) caused a facilitation of the memory retrieval in the inhibitory avoidance task [12]. Ramírez-Lugo et al. reported that intra-insular cortex infusion of scopolamine or the muscarinic receptor subtype 1 selective antagonist pirenzepine before testing had no effects on the retrieval of conditioned taste aversion [39]. Rogers and Kesner assayed the effects of cholinergic modulation on the encoding and retrieval of fear conditioning by intra-hippocampal pre-training infusion of scopolamine or physostigmine (a cholinesterase inhibitor) [42]. They found that scopolamine disrupted the encoding but not the retrieval of the fear conditioning, and physostigmine disrupted the retrieval but not the encoding. They also investigated whether the cholinergic system plays a role in the encoding and retrieval of spatial memory using a modified Hebb-Williams maze [41]. Rats were intra-hippocampus injected with scopolamine or physostigmine 10 min before testing for each day. The number of errors made per day per group was used as the measure of learning. Encoding was assessed by the average number of errors made on the first five trials of day 1 compared to the last five trials of day 1; whereas the average number of errors made on the first five trials of day 2 compared to the last five trials of day 1 was used to assess retrieval. The similar results were obtained—the scopolamine group showed a deficit in the encoding but not the retrieval of the spatial memory, and the physostigmine group showed a deficit in the retrieval but not the encoding. That indicates the cholinergic muscarinic system in the hippocampus has a negative role on the retrieval process of memory. These inconsistent results about the roles of the cholinergic system on the retrieval of memory may due to different brain areas and different muscarinic receptor subtypes which the compounds act on.
In the present study, we inject non-selective muscarinic antagonist scopolamine peripherally 20 min before training or testing to see whether the cholinergic modulation has effects on the acquisition or retrieval of spatial memory by water maze task and fear memory by inhibitory avoidance task, if any, positive or negative. Note that the peripheral injection of scopolamine will exert its effects on entire central nervous system. If the cholinergic system plays a role in the memory retrieval, the retrieval process would be very likely affected by scopolamine. We find that the cholinergic system is essential for the acquisition of both spatial memory and fear memory. As for the memory retrieval, the cholinergic system has a positive role in the retrieval of spatial memory, because mice injected with scopolamine 20 min before the testing in the water maze show impaired spatial memory retrieval. Whereas injection of scopolamine 20 min before the testing in the inhibitory avoidance task does not cause memory retrieval deficits. That indicates the cholinergic system is not essential for the retrieval of fear memory.
Section snippets
Animals
Male C57BL/6J mice of 8 weeks old were purchased from Shanghai Slack Experimental Animal Center. Animals were housed in an ambient temperature of 22–23 °C with a 12-h light/dark cycle with lights on at 08:00 a.m. and had access to food and water ad libitum. The animals were acclimatized to laboratory conditions for a week before all tests. Animal care and all procedures for animal experiments conform to the guidelines of the Animal Care and Use Committee of Guangzhou Biomedical and Health
Scopolamine impairs the acquisition of spatial memory
Statistical analyses reveal a significant main effect of Treatment and a significant interaction of Treatment × Day for latency to reach the platform (F(3, 28) = 11.85, p < 0.001; F(12, 112) = 5.07, p < 0.05; see Fig. 1A), in which animals receiving 1 mg/kg scopolamine injection have longer latencies to the platform, as compared to controls, on day 3 (p < 0.05); animals receiving 2 mg/kg scopolamine injection have longer latencies to the platform, as compared to controls, on days 2–5 (p < 0.05); animals
Discussion
There are some neurobiological and behavioral theories about the mechanisms that underlie the retrieval process of memory [6], [27]. The hippocampus plays a central role in spatial learning and memory [14], [33] and has long been implicated as an important brain area for memory consolidation [17], [35]. It has been addressed that the hippocampus is also important for the retrieval of spatial memory [34]. Riedel et al. [40] investigated the role of the hippocampus in the memory retrieval. First,
Acknowledgment
This work was supported by grants NSFC 30700213 and 973 grant 2007CB947804.
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