Bedeutung einer Beeinträchtigung der D2- und D3-vermittelten dopaminergen Transmission für die motorische Aktivität und das motorische Lernverhalten im Mausmodell

The significance of an impairment of the D2-/D3-mediated dopaminergic transmission for motor activity and motor learning in mice

by Kenan Hasan
Doctoral thesis
Date of Examination:2015-06-29
Date of issue:2015-06-29
Advisor:Dr. Florian Klinker
Referee:Prof. Dr. David Liebetanz
Referee:Prof. Dr. André Fischer
Referee:Prof. Dr. Rainer Mausberg
Persistent Address: http://dx.doi.org/10.53846/goediss-5128

 

 

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Abstract

English

We investigated the locomotor activity and motor learning in running wheel experiments in mice under influence of the dopaminergic system. We evaluated an impairment of the D2 function by using knockout mice and after pharmacological Blockade of the D2 receptor and a lack of D3 function by using D3 knockout mice with and without influence of the dopaminergic system by dietary-induced iron deficiency. A reduction of the D2 receptor function in the D2 knockout mouse or after injection of D2 receptor antagonist raclopride resulted in a significant limitation of all parameters in the normal running wheel. The reduced activity was mainly evident in the quantity of Runs, and much less in a reduced maximum speed, which argues against a purely motor deficit like in Parkinsonoid-diseases. Since the use of the running-wheel (in contrast to habitual movement) requires a high level of motivation, the impairment of the D2 system at the interface between motivation and motor skills leading to a reduced drive to motor activity is a traceable explanation. In the second experiment, we examined the effects of iron deficiency and a lack of the D3 receptor on motor activity and motor learning. An iron-restricted diet led in D3 Knockout mice as well as in wild-type controls to a reduction in the total distance with an unaltered maximum speed. According to previous studies an anemia-induced effect is unlikely to explain theses results. The combination of iron deficiency and lack of D3 receptor resulted in a delay of learning of the new pattern in the complex running wheel, while the single deficiencies did not affect the learning performance. Thus, although activation of the D3 receptor inhibits the learning process in healthy mice, a lack of D3 receptor in coexisting iron deficiency causes additional learning deficits. 
Keywords: motor learning; dopamine; d2 receptor; d3 receptor; running wheel
Schlagwörter: Dopamin; Motorisches Lernen; D2-Rezeptor; D3-Rezeptor; Laufrad
 
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