Levodopa ameliorates learning and memory deficits in a murine model of Alzheimer’s disease

Ambrée, Oliver; Richter, Helene; Sachser, Norbert; Lewejohann, Lars; Dere, Ekrem; de Souza Silva, Maria Angelica; Herring, Arne; Keyvani, Kathy; Paulus, Werner; Schäbitz, Wolf-Rüdiger

doi:10.1016/j.neurobiolaging.2007.11.010

« Previous Next »Neurobiology of Aging
Volume 30, Issue 8 , Pages 1192-1204, August 2009

Levodopa ameliorates learning and memory deficits in a murine model of Alzheimer’s disease

Oliver Ambrée
- Department of Behavioural Biology, University of Münster, Badestrasse 9, D-48149 Münster, Germany
- Corresponding author. Tel.: +49 251 83 21014; fax: +49 251 83 23896.
Helene Richter
- Department of Behavioural Biology, University of Münster, Badestrasse 9, D-48149 Münster, Germany
Norbert Sachser
- Department of Behavioural Biology, University of Münster, Badestrasse 9, D-48149 Münster, Germany
Lars Lewejohann
- Department of Behavioural Biology, University of Münster, Badestrasse 9, D-48149 Münster, Germany
Ekrem Dere
- Institute of Physiological Psychology and Center for Biological and Medical Research, Heinrich-Heine University, D-40225 Düsseldorf, Germany
Maria Angelica de Souza Silva
- Institute of Physiological Psychology and Center for Biological and Medical Research, Heinrich-Heine University, D-40225 Düsseldorf, Germany
Arne Herring
- Institute of Neuropathology, University Hospital Münster, Domagkstrasse 19, D-48149 Münster, Germany
Kathy Keyvani
- Institute of Neuropathology, University Hospital Münster, Domagkstrasse 19, D-48149 Münster, Germany
Werner Paulus
- Institute of Neuropathology, University Hospital Münster, Domagkstrasse 19, D-48149 Münster, Germany
Wolf-Rüdiger Schäbitz
- Institute of Neurology, University Hospital Münster, Albert-Schweitzer-Strasse 33, D-48149 Münster, Germany
- Corresponding author. Tel.: +49 251 83 45235; fax: +49 251 83 48181.

Received 30 May 2007; received in revised form 1 November 2007; accepted 9 November 2007. published online 13 December 2007.

Abstract

Dopamine plays an important role in learning and memory processes. A deficit of this neurotransmitter as it is apparent in Alzheimer’s disease (AD) may contribute to cognitive decline, a major symptom of AD patients. The aim of this study was to elucidate whether or not stimulation of the dopaminergic system leads to an improvement of cognitive function and reduction of non-cognitive behavioral alterations in a murine model of AD.

Transgenic and wild type male mice of the TgCRND8 line were treated either with the dopamine precursor levodopa or vehicle and tested in two learning tasks, the object-recognition task and the Barnes maze test. Additionally 24 h spontaneous behavior in the home cage was analyzed.

In both memory tasks wild type mice performed significantly better than transgenics. However, transgenics treated with levodopa showed a significant object recognition memory and improved acquisition of spatial memory in the Barnes maze compared to vehicle treated transgenics. Concerning spontaneous behavior transgenic mice performed much more stereotypies than wild types. However, there was a trend for reduced stereotypies in the levodopa group in the time the drug was active. Neurochemical analysis revealed elevated levels of dopamine in the neostriata and frontal cortices and reduced levels in the hippocampi of transgenic mice compared to wild types. Thus cognitive deficits and stereotypies may be due to changes in the dopaminergic system as they could be ameliorated by levodopa treatment, that might also have a therapeutic significance for AD.

Keywords: Alzheimer’s disease, Dopamine, l-DOPA, Transgenic mice, TgCRND8, Learning and memory, Barnes maze, Spatial learning, Object recognition, Stereotypic behavior