Sep 1, 1996 - study, the latencies displayed by the 19°C and 25°C groups on the first training day were comparable. It can be reasoned, therefore, that.
European Journal of Neuroscience, VoE. 9, pp. 637442, 1997
0 European Neuroscience Association
Experience-dependent Facilitating Effect of Corticosterone on Spatial Memory Formation in the Water Maze Carmen Sandi, Maria Loscertales and Carmen Guaza Psychobiology Research Group, Cajal Institute, CSIC, Avda. Doctor Arce 37, 28002 Madrid, Spain Keywords: glucocorticoid, memory, rat, stress
Abstract Stress-related adrenal steroid hormones modulate brain and cognitive function. Electrophysiologicalstudies, including primed burst potentiation and long-term potentiation, have indicated concentration-dependent inverted U-shape effects of corticosterone in hippocampal function and plasticity. Here, we explored the role of corticosterone in the consolidation and long-term retrieval of spatial learning in the Morris water maze task in rats. We postulated that corticosterone actions might be experience-dependent with regard to stimulus intensity, such as differential water temperatures. Indeed, rats trained at 19°C showed a quicker rate of acquisition and better long-term retention than rats trained at 25°C water. In addition, post-training corticosterone levels, on the first training day, were significantly higher in rats in the 19°C group than in the 25°C group. Performance of rats trained at 25"C, but not at 19"C, water was improved by injecting them i.p. with corticosterone immediately after each training session. Thus, the effect of exogenously administered corticosterone appears to be experiencedependent, with the experience-inducedcorticosterone concentrations as a critical factor determining the cognitive consequences of steroid treatment. Therefore, this work indicates a facilitating corticosterone action, during the post-training period, on the neural mechanisms determining the strength of information storage under acute, physiological conditions. Introduction Stress, and stress-related adrenal steroid hormones, modulate brain and cognitive function (McEwen and Sapolsky, 1995). At the brain, corticosteroids act primarily through binding to two intracellular receptors, the mineralocorticoid receptor (MR) and the glucocorticoid receptor (GR). Particular attention is being devoted to the functional role of corticosteroid actions in the hippocampus, due to the role of this area in learning and memory processes (O'Keefe and Nadel, 1978; Moms et al., 1982). Corticosteroids were shown to modulate, in an inverted U-shaped manner, the expression of hippocampal longterm potentiation (LTP) (Pavlides et al., 1993, 1995; Kerr et al., 1994) and primed burst potentiation ( P B P ) (Bennet et al., 1991; Diamond et al., 1992, 1994), two forms of synaptic plasticity which may underlie memory formation. Thus, either removal of endogenous glucocorticoids, or stress levels of corticosteroids, suppressed hippocampal potentiation, whereas steroid concentrations corresponding to a basal physiological state facilitated such potentiation. According to data from electrophysiological studies on LTP (Pavlides et al., 1995) and neuronal excitability (Joels and de Kloet, 1992), these concentration-dependent biphasic actions are due to opposing roles for each corticosteroid receptor type on synaptic plasticity, i.e. with MRs facilitating and GRs suppressing hippocampal potentiation. The relevance of these corticosteroid actions on synaptic plasticity for the mechanisms of memory formation is not clear. Animal studies have focused on spatial memory for its dependence upon hippocampal
functioning (O'Keefe and Nadel, 1978). In particular, the Moms water maze task (Morris, 1984), which is widely used to study the neurobiological basis of hippocampal-dependent spatial memory, is dependent upon corticosteroids. Removal of endogenous corticosterone through adrenalectomy impairs spatial memory performance in this task (Oitzl and de Kloet, 1992), as also shown for a radial arm maze (Vaher et al., 1994). Central administration of specific antagonists for each receptor type also interfered with spatial learning in the water maze (Oitzl and de Kloet, 1992). Therefore, these results support a positive effect of corticosteroids in spatial memory formation. Might stress-related corticosterone levels be able to modulate as well performance on this task? Although corticosterone administration was shown to potentiate memory formation in different tasks and species (Flood et al., 1978, Micheau et al., 1985; Sandi and Rose, 1994a; Roozendal and McGaugh, 1996), there is also evidence for deleterious effects (Bohus and de Wied, 1980). Since water temperature appears to influence the acquisition rate of the water maze task (Moms, 1984; Vanderwolf, 1991), as well as determining corticosteroid involvement in another swimming-based task, the Porsolt swim test (Peeters et aL, 1992), we postulated that: (i) differential performance at different water temperatures might be related to differential corticosterone release at training; and (ii) a possible modulatory action of corticosterone administration might be experience-dependent as for water temperature. Therefore, this study ~
Correspondence to: C. Sandi, Department of Psychobiology, Universidad Nacional de Educacion a Distancia, PO Box 60.148, Ciudad Universitaria s/n, 28040
Madrid, Spain Received I 1 September 1996, accepted 31 October I996
638 Corticosterone and spatial learning
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FIG.1. Effects of training rats at different water temperatures on the rate of acquisition (3 training days; left panel) and long-term retrieval (7 days post-training; right panel) of spatial learning in the water maze. Data are the means 2 SEM from six to I0 rats per group. *P < 0.05 versus water 25°C.
was designed to assess these hypotheses, by evaluating (i) performance and blood corticosterone levels of rats trained in the water maze at different water temperatures; and (ii) the effect of corticosterone administration on spatial memory formation under different water temperatures.
Materials and methods Animals Adult male Wistar rats (250-300 g) from our in-house colony were used. They were housed four to five per cage (45 X 25 X 20 cm) under temperature (22 ? 2" C) and light (12:12 light-dark cycle; lights on at 7 a.m.) controlled conditions and had free access to food and water. Experiments were always conducted between 0900 and 1400 h. Animal care procedures were conducted in accordance with the guidelines set by the European Community Council Directives (86/609/EEC). Drug administration Corticosterone (Sigma, Spain; 5 mgkg) was dissolved in absolute ethanol and subsequently diluted in 0.9% saline, with final concentration containing
