Gewählte Publikation:
Dischinger, U.
Relevance of hormones and peptides to food intake: Effects of JNJ-31020028
[ Diplomarbeit ] Medical University of Graz; 2011. pp. 78
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- Autor*innen der Med Uni Graz:
- Betreuer*innen:
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Holzer Peter
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Singewald Evelin
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- Abstract:
- Anroexia nervosa is one of the most severe diseases in psychiatry. A lack of pharmaco-therapeutical possibilities is one reason for this fact. Therefore it is of great concern to gain further information about the pathophysiological background of anorexia nervosa and to find appropriate animal models, with the aim to determine new pharmacological possibilities and to test their effects in a preclinical environment.
In the first part of this paper, a review of several peptides and hormones in the regulation of ingestion and their impact in anorexia nervosa is given. Discussed are neuropeptide Y, agouti-related peptide, melanocortin system, corticotropin-releasing factor, peptide YY, the hormones leptin and ghrelin, nitric oxide and the endocannabinoid system. Regarding food intake, these hormones/peptides can be classified as orexigenic, meaning food intake stimulating, or anorexigenic. However, this classification is not generally suitable, as is shown here for the case of neuropeptide Y. At the beginning of the first part, several animal models which might be appropriate for preclinical anorexia nervosa research are presented. Attention is focused especially on the activity-stress model by Routtenberg and Kuznesof. This model imitates among other things a hyperactive behaviour which is often observed in anorexia nervosa patients.
The second part of this paper reports on the effects of the Y2 receptor antagonist JNJ-31020028 in mice regarding food and water intake as well as activity. This substance was injected intraperitoneally to female mice in three experimental approaches. The first and second approach only differed in substance dose (10 mg/kg, resp. 20 mg/kg) and the mice received food ad libitum, while in the third approach (10 mg/kg) the access to food was restricted to three hours a day. Mice of the strain DBA/2 were used because this strain was reported to become hyperactive in case of diet-restriction. The weight of the mice was measured at defined points in each trial, while the LabMaster system was used to measure feeding, drinking and activity over the whole time. An effect of JNJ-31020028 to increase food intake was shown in the first approach (10 mg/kg), an effect that was not present in the second approach with a twofold dose of the substance (20 mg/kg). A significant effect of JNJ-31020028 on the activity level of the experimental animals was not seen. Thus, any role of neuropeptide Y acting via Y2 receptors in anorexia nervosa remains questionable.