Research report
The effects of a mild stressor on spontaneous alternation in mice

https://doi.org/10.1016/S0166-4328(00)00285-0Get rights and content

Abstract

Adult mice of the C57BL/6J strain were subjected to an acute mild stress at different periods before the choice trial of a spontaneous alternation test. The stressful event was either inescapable (forced exploration in a brightly lit open field) or escapable (temporary entries into an adjacent dark chamber). While unstressed control mice alternated above chance in each condition, mice subjected to inescapable stress did not alternate when forced exposure to the open field occurred during the entire retention interval. The same effect was seen when forced exposure to the open field occurred after a post-forced trial delay period. However, no change in the alternation rate was observed when the inescapable stress occurred before the forced trial, or if the delay intervened between the stressful event and the choice trial. The escapable stressful event had no effect on spontaneous alternation. These results indicate the role of cognitive mediation in the behavioral effects of inescapable stress, causing either a retrieval deficit or neophobia.

Introduction

The deleterious effects of stressful experiences on cognitive functions have been investigated under many experimental conditions in both humans and animals [5], [18], [24], particularly in memory processes [8], [10], [12], [20], [22], [37]. The psychobiological consequences of stressful events can be reduced after administration of benzodiazepines [14] or changes in environmental conditions [41]. Some of the effects of stressful events may be mediated by the direct action of glucocorticoids on brain functions, particularly in the hippocampus, a region with a high density of glucocorticoid receptors [25] and crucially involved in spatial memory [17], [28], [31], [32], [33], [39]. Increases of plasma glucocorticoid concentrations either by endogenous [23], [34], [35], [40] or exogenous [3], [4], [7], [26], [30] means or the administration of glucocorticoid receptor agonists [9], [42] impaired different learning tests. Moreover, chronic corticosterone administration impaired spontaneous alternation [2]. Nevertheless, chronic corticosterone administration did not cause spatial learning deficits so severe as a prolonged psychosocial stressful event, indicating that corticosterone is not the sole mediator of the behavioral consequences of stressful events [18]. On the other hand, short-term glucocorticoid administration sometimes facilitates learning, for example during active or passive avoidance learning [11] and the same effect can be seen after inescapable stress as well, for example during acquisition of the classically conditioned eyeblink response [38] and spatial learning [21].

In the present study the effects of a mildly stressful event (exposure to a novel bright lit open field), as indicated by increases of plasma concentrations of corticosterone, were evaluated on two-trial spontaneous alternation. After a forced trial to one of two arms in a T-maze, mice have a strong tendency to choose the opposite arm. This behavior requires spatial working memory and is sensitive to bilateral lesions of widespread areas of the brain including the hippocampus [6], [13], [17]. The stressful event occurred at different periods but always before the choice trial. It could either be escapable (temporary entries into an adjacent dark chamber) or inescapable (continuous exposure). By such means we wished to investigate whether a stressful event impairs storage or retrieval processes and whether a differential effect can be demonstrated as a function of cognitive mediation of this event.

Section snippets

Animals

The animals used in this study were 120 male mice of the C57BL/6 strain, 3–5 months old, weighing between 27 and 32 g, obtained from our own colony. They were reared five per cage in standard conditions (12 h light/12 h dark: 08:00–20:00/20:00–08:00; 20–22°C; food and water available ad libitum). The animals were regularly handled before the experiment in order to minimize handling-related stress and then split into three groups: escape stress, inescapable stress, and unstressed controls.

Open field

The

Plasma corticosterone concentrations

A significant group effect was seen for plasma corticosterone concentrations immediately after exposure to the open field during 12–14 min (F(2,27)=21.709, P<0.0001) or after this 12–14 min exposure was followed by a 10 min delay period spent in the home cage (F(2,27)=16.709, P<0.0001). Tukey HSD test indicated that both the escapable (P<0.001) or the inescapable (P<0.001) stressful event increased corticosterone levels either with or without the delay interval (Fig. 2).

Spontaneous alternation

Irrespective of the

Discussion

The alternation rate of unstressed controls was significantly above chance irrespective of the retention interval, lasting up to 24 min. Mice can alternate even at retention intervals of at least 1 h [6]. The presence of alternation presupposes an intact short-term memory for the previously visited arm [17], [32], [33] and the motivation to explore the novel arm instead of the previously explored arm.

The purpose of the present study was to evaluate the effects of a mildly stressful event

References (42)

  • D. Mitchell et al.

    Arousal and T-maze choice behavior in mice: a convergent paradigm for neophobia constructs and optimal arousal theory

    Learn. Motiv.

    (1984)
  • D.S. Olton et al.

    Spatial memory and hippocampal function

    Neuropsychology

    (1979)
  • R.M. Sapolsky et al.

    Corticosterone receptors decline in a site-specific manner in the aged rat brain

    Brain Res.

    (1983)
  • T. Shimada et al.

    The modified light/dark transition test in mice: evaluation of classic and putative anxiolytic and anxiogenic drugs

    Gen. Pharmacol.

    (1995)
  • M.N. Starkman et al.

    Hippocampal formation volume, memory dysfunction, and cortisol levels in patients with Cushing's syndrome

    Biol. Psychiatry

    (1992)
  • B.E. Beckwith et al.

    Dose-dependent effects of hydrocortisone on memory in human males

    Physiol. Behav.

    (1986)
  • J. Benton et al.

    Steroids and apparent cerebral atrophy on computed tomography scans

    J. Comput. Assist. Tomogr.

    (1978)
  • J.D. Bremner et al.

    Functional neuroanatomical correlates of the effects of stress on memory

    J. Trauma. Stress

    (1995)
  • J. Caston et al.

    Delayed spontaneous alternation in intact and cerebellectomized control and Lurcher mutant mice: differential role of cerebellar cortex and deep cerebellar nuclei

    Behav. Neurosci.

    (1997)
  • L.D. Clark et al.

    Preliminary observations on mental disturbances occurring in patients under therapy with cortisone and ACTH

    New Engl. J. Med.

    (1952)
  • C.D. Conrad et al.

    Chronic stress impairs rat spatial memory on the Y maze, and this effect is blocked by tianeptine pretreatment

    Behav. Neurosci.

    (1996)
  • Cited by (41)

    • Extract of Xylopia aethiopica and its kaurene diterpene, xylopic acid, improve learning and memory in mice

      2022, IBRO Neuroscience Reports
      Citation Excerpt :

      Spatial recognition memory was measured during this trial. To eliminate olfactory traces of previous maze users which had the tendency to affect the percentage alternation in the Y-maze (Bats et al., 2001; Hughes, 2004), 70% ethanol was used to clean the maze in between trials. The Morris water maze test was carried out according to methods described by Morris (1981), Morris et al. (1986), Nunez (2008), Sun and Alkon (2004), and Barnhart et al. (2015), to assess hippocampal-dependent spatial/place learning and working memory.

    • Acute restraint stress redirects prefrontal cortex circuit function through mGlu<inf>5</inf> receptor plasticity on somatostatin-expressing interneurons

      2022, Neuron
      Citation Excerpt :

      We first examined restraint stress effects on working memory using a spatial navigation task (Figure 8A). Acute stress, and other manipulations that disrupt working memory, decreases a rodent’s ability to successfully alternate through the three distinct arms of a Y-maze (e.g., ABC, not ABA) (Bats et al., 2001; Kim et al., 2018; Ohgidani et al., 2016). Although WT mice displayed impaired spatial alternation following restraint stress, performance in littermate SST-mGlu5−/− mice was not affected (Figure 8B).

    • Spatial working memory is disparately interrelated with social status through different developmental stages in rats

      2022, Behavioural Brain Research
      Citation Excerpt :

      This nonappetitive task makes use of the intrinsic tendency of rodents to explore “novel” areas more than “known” ones in the absence of rewarding stimuli [70]. This procedure was of choice due to avoiding the need for extensive training sessions or use of reinforcers, leaving the motivational state of the animals relatively unscathed [68,71–75]. The maze consisted of a circular black tank (180 cm in diameter and 85 cm high) filled with tap water (22 ± 1 °C) to a depth of 40 cm, in a dimly lit room, without adding any dye to the water as the escape platform used was made of transparent Plexiglas.

    View all citing articles on Scopus
    View full text