Excitotoxic median raphe lesions aggravate working memory storage performance deficits caused by scopolamine infusion into the dentate gyrus of the hippocampus in the inhibitory avoidance task in rats.

E Babar,T Özgünen,E Melik

doi:10.1590/s0100-879x2002000400012

E Babar, T Özgünen + Show 1 more

Open Access

https://doi.org/10.1590/s0100-879x2002000400012

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Abstract

The interactions between the median raphe nucleus (MRN) serotonergic system and the septohippocampal muscarinic cholinergic system in the modulation of immediate working memory storage performance were investigated. Rats with sham or ibotenic acid lesions of the MRN were bilaterally implanted with cannulae in the dentate gyrus of the hippocampus and tested in a light/dark step-through inhibitory avoidance task in which response latency to enter the dark compartment immediately after the shock served as a measure of immediate working memory storage. MRN lesion per se did not alter response latency. Post-training intrahippocampal scopolamine infusion (2 and 4 microg/side) produced a more marked reduction in response latencies in the lesioned animals compared to the sham-lesioned rats. Results suggest that the immediate working memory storage performance is modulated by synergistic interactions between serotonergic projections of the MRN and the muscarinic cholinergic system of the hippocampus.

Highlights

There is considerable evidence suggesting that the interactive processes between the serotonin (5-HT) and acetylcholine (ACh) systems are severely affected in a majority of Alzheimers disease cases [1,2,3]
In the present study, using a single-trial step-through inhibitory avoidance task, we examined the effects of neurotoxic lesions of the median raphe nucleus (MRN) on immediate memory deficits resulting from post-training scopolamine infusion into the dentate gyrus of the dorsal hippocampus which is a MRN-innervated area [24], and thereby tried to determine if the MRN-serotonergic system regulates immediate working memory storage performance by interacting with the septohippocampal muscarinic cholinergic system
The present results demonstrate that in rats with an intact cholinergic system, neurotoxic damage to the polygonal serotonergic cell bodies in the MRN region had no effect on immediate storage of working memory in the inhibitory avoidance task per se

Summary

Introduction

There is considerable evidence suggesting that the interactive processes between the serotonin (5-HT) and acetylcholine (ACh) systems are severely affected in a majority of Alzheimers disease cases [1,2,3]. The abnormalities in interactive neurotransmitter processes may be a factor causing cognitive impairments such as working memory deficits in this disease [4,5]. It is well known that the hippocampus is a critical structure for the interaction of 5-HT and ACh systems and for the mediation of working memory [8,9,10,11,12]. It has been proposed that the interactions between the septohippocampal 5-HT and ACh in the modulation of learning and memory may depend on serotonergic origins [18,19] and specification of 5-HT receptors [17]. The immediate memory in a single-trial inhibitory avoidance test is identified as working memory [21,22,23]

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