Elsevier

Physiology & Behavior

Volume 91, Issue 5, 15 August 2007, Pages 652-657
Physiology & Behavior

Brain serotonin depletion impairs short-term memory, but not long-term memory in rats

https://doi.org/10.1016/j.physbeh.2007.03.028Get rights and content

Abstract

Intracerebroventricular injection of 5,7-dihydroxytryptamine (5,7-DHT) (150 μg; 4.5 μl/ventricle), a serotonergic neurotoxin, significantly decreased spontaneous alternation in Y-maze task and working memory in radial 8 arm-maze task, suggesting effects on short-term memory, without affecting long-term memory, explored by reference memory in radial 8 arm-maze task and step-through latency in multi-trial passive avoidance task. Parachlorophenylalanine (PCPA) (3 days treatment 200 μg, i.c.v.), a serotonin synthesis inhibitor, did not impair step-through-latency in multi-trial passive avoidance task, suggesting no effects on long-term memory. These results suggest that serotonin, among other neurotransmitters, play an important role in cognitive functions, especially short-term memory.

Introduction

Previous studies have suggested that serotonin may be involved in the modulation of brain functions such as appetite, thermoregulation, aggression and sexual behavior [1], [2]. Serotonin is also known to be associated with various pathophysiological processes, including depressive disorders, schizophrenia and dementia [2]. Serotonin also appears to facilitate synapse formation and maintenance, and thereby to modulate the net number of synapse in the developing and mature brain [3], [4], [5].

The serotonergic neural system derives mainly from neurons in the dorsal and ventral raphe nuclei with projection to virtually every brain region that subserves cognition. There is neurochemical and pathological evidence of a decline in the function of the serotonergic system of Alzheimer's disease (AD) patients [6], [7]. It has been proposed that the abnormalities in the serotonergic system in AD may be related to behavioral disturbance such as depression, aggressive behavior and anxiety rather to cognitive dysfunction [8]. However, studies with experimental animals have provided evidence for the serotonergic system being involved in cognitive processes [9], [10]. For example, lesions of raphe nuclei, induced by 5,7-DHT, impair delayed spatial alternation in a T-maze at a delay (60 s) but not at shorter delays (5 and 30 s) [11], indicating an impairment in working memory.

5,7-DHT lesion of the dorsal raphe nuclei may also impair object recognition but not affective behavior and corticosterone response to stressor in the rat, indicating an impairment in object memory [12]. There are also studies which have shown that intracerebroventricular 5,7-DHT lesion disrupts acquisition of working memory task rules but not performance once learned, locomotion exploration and place recall in the rat, suggesting that the serotonergic system is important in the acquisition of working memory and exploratory behavior [13], [14]. However, there are also studies which have shown that manipulations at the serotonergic system alone do not cause changes in cognitive function per se [15], [16], [17], [18]. Thus, the role of serotonergic system in cognition is rather controversial.

The aim of the present work was to study the effects of lesions of different serotonergic neurons by means of i.c.v. administration of 5,7 -DHT, acting as a serotonergic neurotoxin, and PCPA, which blocks the synthesis of serotonin, on learning and memory processes evidenced by means of Y-maze task, radial 8 arm-maze task and multi-trial passive avoidance task. Both PCPA and 5,7-DHT treatments are led to a severe decrease in the central serotonin level. Our data suggest that serotonin plays an important role in learning and memory processes.

Section snippets

Animals

Male Wistar rats weighing 200–250 g at the start of the experiment were used. The animals were housed in a temperature- and light-controlled room (22 °C, a 12-h cycle starting at 08:00 h) and were fed and allowed to drink water ad libitum. Rats were treated in accordance with the guidelines of animal bioethics from the Act on Animal Experimentation and Animal Health and Welfare Act from Romania and all procedures were in compliance with the European Council Directive of 24 November 1986

Effect of 5,7-DHT-induced serotonergic lesion on learning and memory

I.c.v. administration of 5,7-DHT (150 μg, 4.5 μl/ventricle) evidenced a significant impairment of short-term memory, explored by means of Y-maze task, indicated by a decrease of spontaneous alternation percentage (F(1,14) = 17.8, p < 0.0008) (Fig. 1). This effect could not be attributed to decreased motor activity, because the number of arms entries was not significantly changed (F(1,14) = 0.01, p > 0.05] (Fig. 1).

Serotonin depletion with 5, 7-DHT does not produce a significant change in long-term

Discussions

Previous studies have suggested the controversial role of serotonergic systems in learning processes. For example, serotonergic lesions have been reported to have no effect [24], [25], facilitate [24], [26] or impair [13], [14], [26] performance in various learning tasks.

Our results showed that serotonergic depletion by means of 5,7-DHT or PCPA induce a board spectrum of behavioral effects. Brain serotonin depletion by means of 5,7-DHT induced a significant decrease in short-term memory

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