Elsevier

Behavioural Brain Research

Volume 175, Issue 1, 25 November 2006, Pages 183-188
Behavioural Brain Research

Research report
Further evidence that anxiety and memory are regionally dissociated within the hippocampus

https://doi.org/10.1016/j.bbr.2006.08.021Get rights and content

Abstract

The hippocampus has been implicated in the regulation of anxiety and memory processes. Nevertheless, the precise contribution of its ventral (VH) and dorsal (DH) division in these issues still remains a matter of debate. The Trial 1/2 protocol in the elevated plus-maze (EPM) is a suitable approach to assess features associated with anxiety and memory. Information about the spatial environment on initial (Trial 1) exploration leads to a subsequent increase in open-arm avoidance during retesting (Trial 2). The objective of the present study was to investigate whether transient VH or DH deactivation by lidocaine microinfusion would differently interfere with the performance of EPM-naive and EPM-experienced rats. Male Wistar rats were bilaterally-implanted with guide cannulas aimed at the VH or the DH. One-week after surgery, they received vehicle or lidocaine 2.0% in 1.0 μL (0.5 μL per side) at pre-Trial 1, post-Trial 1 or pre-Trial 2. There was an increase in open-arm exploration after the intra-VH lidocaine injection on Trial 1. Intra-DH pre-Trial 2 administration of lidocaine also reduced the open-arm avoidance. No significant changes were observed in enclosed-arm entries, an EPM index of general exploratory activity. The cautious exploration of potentially dangerous environment requires VH functional integrity, suggesting a specific role for this region in modulating anxiety-related behaviors. With regard to the DH, it may be preferentially involved in learning and memory since the acquired response of inhibitory avoidance was no longer observed when lidocaine was injected pre-Trial 2.

Introduction

The hippocampus has a long established-role in spatial learning and memory [24], [28]. It may also regulate defensive behaviors related to anxiety [4]. Electrolytic or excitotoxic lesions of the hippocampus produce anxiolytic-like behaviors in elevated mazes and social interaction tests [2], [10]. Moreover, it is proposed that anxiolytic-like drugs induce their effects by acting on a behavioral inhibition system that includes the hippocampus [15].

There is considerable evidence to suggest that the hippocampus may be differentiated into dorsal (DH) and ventral (VH) poles [4], [27]. The precise contribution of these two regions on anxiety and memory, however, still remains a matter of debate. With regard to the former process, research has frequently focused on avoidance behavior scored in the elevated plus-maze (EPM) test. Microinjection of the benzodiazepine midazolam into the DH decreased this response [19], [20]. However, anxiolytic-like effects were also reported after either excitotoxic or electrolytic lesions of the VH, but not the DH [16]. VH lesions also reduced anxiety-related responses in the social interaction, the light/dark, the elevated T-maze and the cat-odor exposure tests [18], [26], [32]. These findings suggest that defensive behaviors related to anxiety are preferentially regulated by the VH. In relation to spatial learning aspects, a wealth of evidence suggests that it depends preferentially on DH function [4], [21]. For instance, the degree of impairment of spatial learning in a water-maze correlates with DH, but not VH lesions [22], [23], [33].

The objective of the present study was to further investigate a possible hippocampal regional dissociation regarding the modulation of anxiety and memory processes. Since prior studies have usually assessed this issue by using lesion techniques, the current study adopted acute bilateral lidocaine microinfusion into the VH or the DH to transiently interfere with normal hippocampal activity. In addition, since behavioral measures related to anxiety and memory has been usually assessed by different tests, the present study used the EPM Trial 1/2 protocol. In the EPM test, after the initial (Trial 1) exploration of the whole apparatus, rodents express increased inhibitory avoidance response during retesting (Trial 2). This latter finding is thought to reflect the acquisition of spatial memory related to exploration of potentially dangerous areas of the maze—the open-arms [6], [9]. This approach, therefore, was selected based on its capacity of evaluating either anxiety- and memory-related behavioral responses. Our hypothesis is that lidocaine microinfusion into the VH would interfere with the former whereas the latter responses would be prudentially affected by DH inactivation.

Section snippets

Animals

One-hundred and fifty-five male Wistar rats weighing 250–270 g at the time of testing were housed in pairs in a temperature-controlled room (23 ± 1 °C), under standard laboratory conditions with free access to food and water, and with a 12 h light/12 h dark cycle (lights on at 06:30 h a.m.). Procedures were conducted in conformity with the Brazilian Society of Neuroscience and Behavior guidelines for the care and use of laboratory animals, which are in compliance with international laws and politics.

Results

Pictures showing representative injection sites into the VH and the DH can be seen in Fig. 1. Animals receiving microinjections outside these hippocampal poles (27% and 14%, respectively) were excluded from the analysis.

Discussion

The main experimental findings of the present study are that: (1) lidocaine injected into the VH prior to Trial 1 increased open-arm exploration. No effect was found, however, when the same treatment was given at post-Trial 1 or pre-Trial 2 and (2) lidocaine injected into the DH reduced the open-arm avoidance when given at pre-Trial 2, but not at pre-Trial 1 or post-Trial 1.

These findings are consistent with studies implicating the VH, but not the DH, in the regulation of anxiety-related

Acknowledgments

This work was supported by FAPESP (02/13197-2; 03/13032-6; 04/13197-4). The authors also thank A.P. Padovan, D.C. de Aguiar and J.C. de Aguiar for technical assistance.

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