Advanced

Combined cholinergic and serotonergic denervation of the forebrain produces severe deficits in a spatial learning task in the rat

Nilsson, O G LU ; Strecker, R E ; Daszuta, A and Björklund, A LU (1988) In Brain Research 453(1-2). p.235-246
Abstract

The purpose of the present experiments was to study the effects of a combined cholinergic and serotonergic denervation of the rat forebrain on spatial learning using the Morris water maze task. Experiment 1 compared the acute effects of a radiofrequency lesion of the septum, an intraventricular 5,7-dihydroxytryptamine (5,7-DHT) lesion, and a combined septal plus 5,7-DHT lesion. Although the 5,7-DHT lesion alone did not produce any significant deficits in the water maze task, the lesion greatly potentiated the learning impairments produced by the septal lesion. Thus, the rats with both lesions combined showed severe difficulties in finding the platform and they did not develop any place navigational search strategy. This effect was not... (More)

The purpose of the present experiments was to study the effects of a combined cholinergic and serotonergic denervation of the rat forebrain on spatial learning using the Morris water maze task. Experiment 1 compared the acute effects of a radiofrequency lesion of the septum, an intraventricular 5,7-dihydroxytryptamine (5,7-DHT) lesion, and a combined septal plus 5,7-DHT lesion. Although the 5,7-DHT lesion alone did not produce any significant deficits in the water maze task, the lesion greatly potentiated the learning impairments produced by the septal lesion. Thus, the rats with both lesions combined showed severe difficulties in finding the platform and they did not develop any place navigational search strategy. This effect was not dependent on any effect on swimming ability or locomotor activity. The long-term effects of the combined septal and 5,7-DHT lesion was investigated in experiment 2, where the rats were tested in the water maze both 5 and 24-25 weeks after surgery. In this experiment, the rats showed the same severe deficits in spatial learning in both tests, showing that the impairments remain for long periods and after extended training. The results show that a combination of a cholinergic and a serotonergic denervation of the rat forebrain produces pronounced impairments in spatial learning in the Morris water maze task, and that this effect is long-lasting. This indicates that the recently proposed serotonergic deficit in patients with Alzheimer's disease may contribute importantly to the cognitive disabilities in these patients.

(Less)
Please use this url to cite or link to this publication:
author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
5,7-Dihydroxytryptamine, Animals, Choline O-Acetyltransferase/metabolism, Cholinergic Fibers/enzymology, Female, Frontal Lobe/metabolism, Injections, Intraventricular, Learning/physiology, Motor Activity/physiology, Rats, Rats, Inbred Strains, Reaction Time/physiology, Serotonin/metabolism, Spatial Behavior/physiology
in
Brain Research
volume
453
issue
1-2
pages
235 - 246
publisher
Elsevier
external identifiers
  • scopus:0023876202
  • pmid:3401761
ISSN
0006-8993
DOI
10.1016/0006-8993(88)90163-1
language
English
LU publication?
yes
id
51103be4-1cf9-49d7-a369-39713eaab9f0
date added to LUP
2019-06-25 10:22:04
date last changed
2019-08-26 11:17:26
@article{51103be4-1cf9-49d7-a369-39713eaab9f0,
  abstract     = {<p>The purpose of the present experiments was to study the effects of a combined cholinergic and serotonergic denervation of the rat forebrain on spatial learning using the Morris water maze task. Experiment 1 compared the acute effects of a radiofrequency lesion of the septum, an intraventricular 5,7-dihydroxytryptamine (5,7-DHT) lesion, and a combined septal plus 5,7-DHT lesion. Although the 5,7-DHT lesion alone did not produce any significant deficits in the water maze task, the lesion greatly potentiated the learning impairments produced by the septal lesion. Thus, the rats with both lesions combined showed severe difficulties in finding the platform and they did not develop any place navigational search strategy. This effect was not dependent on any effect on swimming ability or locomotor activity. The long-term effects of the combined septal and 5,7-DHT lesion was investigated in experiment 2, where the rats were tested in the water maze both 5 and 24-25 weeks after surgery. In this experiment, the rats showed the same severe deficits in spatial learning in both tests, showing that the impairments remain for long periods and after extended training. The results show that a combination of a cholinergic and a serotonergic denervation of the rat forebrain produces pronounced impairments in spatial learning in the Morris water maze task, and that this effect is long-lasting. This indicates that the recently proposed serotonergic deficit in patients with Alzheimer's disease may contribute importantly to the cognitive disabilities in these patients.</p>},
  author       = {Nilsson, O G and Strecker, R E and Daszuta, A and Björklund, A},
  issn         = {0006-8993},
  language     = {eng},
  month        = {06},
  number       = {1-2},
  pages        = {235--246},
  publisher    = {Elsevier},
  series       = {Brain Research},
  title        = {Combined cholinergic and serotonergic denervation of the forebrain produces severe deficits in a spatial learning task in the rat},
  url          = {http://dx.doi.org/10.1016/0006-8993(88)90163-1},
  doi          = {10.1016/0006-8993(88)90163-1},
  volume       = {453},
  year         = {1988},
}