Die Bedeutung des zentralen Serotonin-1A-Rezeptors für das Nahrungsaufnahmeverhalten der Maus

- The relevance of the central serotonin1A-receptor for the feeding behavior of the mouse -
The success of pharmacotherapy in disorders of eating behavior has been insufficient. This is why the complex regulation of food intake is in the focus of research for decades. The involved multipart regulatory systems show a close interaction with each other. Because of this the exact mechanisms have not yet been elucidated in detail. Although it is ensured that the central serotonergic system exerts an influence on the regulation of food intake, the impact of the serotonin (5-HT)1A receptor is not completely understood.
The present work enlarges the knowledge of the participation of the serotonergic system, and in particular of the 5-HT1A-receptor in the regulation of food intake in the mouse while using various tests. In the experiments the food intake of two mouse-strains, NMRI and C57BL/6, and the transgenic mouse L35, with an overexpression of the postsynaptic 5-HT1A-receptor, after a systemic injection of the 5-HT1A-receptor-agonist 8-OH-DPAT has been investigated. The tests were conducted under three different conditions. First, mice have been fed ad libitum while the test started in the light phase. Second, mice have been food deprived for 16h and again tested during the light phase. Last, mice have been fed ad libitum and the experiment started at the beginning of the dark phase. With the help of the 5-HT1A-receptorantagonist WAY100635 an 8-OH-DPAT-effect via the 5-HT7- and the alpha2-adrenergic-receptor should be ruled out.
After systemic injection of 8-OH-DPAT the amount of eaten food has been detected in different intervals (0-30min, 30min-60min, 60min-120min). In addition to this, water intake and motor activity in the home cage have been determined. For further characterization of the 8-OH-DPAT induced effects on food intake the microstructure of feeding was used.
As the most important result an effect of 8-OH-DPAT on food intake in mice has been shown. However, this effect was depending on the mouse strain, sex, feeding status, age, and time of testing. Specifying this, male ad libitum fed NMRI mice show a hyperphagia but C57BL/6 males do so only in the adult group and after a hypophagic response at the beginning of the trial. This implicates strain differences. Because of tests with the 5-HT1A-receptor-antagonist WAY100635 it is clear that the effects of 8-OH-DPAT are due to its impact at the 5-HT1A-receptor.
The assessment of the effects of wild type animals, and transgenic mice shows a distinct effect of the postsynaptic 5-HT1A-receptor on food intake for all tested transgenic groups. First, the injection of NaCl leads to a different “basal”-food intake. This could be shown due to reduced food intake 30min-60min after testing begun. Second, food intake was influenced by application of 8-OH-DPAT. The degree of influence has been varied depending on gender and age. For the first time, a hyperphagia in female mice has been shown. Conversely, in adult transgenic mice there was no effect of 8-OH-DPAT on food intake. Further tests have to clarify whether and to which extend the postsynaptic 5-HT1A-receptor is subject of changes during maturation.
The results of the present work allow conclusions about the importance of the serotonergic system in general and of the 5-HT1A-receptor in particular in the regulation of food intake. The presented impact of the postsynaptic 5-HT1A-receptor on food intake clearly shows the complexity of the regulation of food intake.