Dopaminergic and brain-derived neurotrophic factor signalling in inbred mice exposed to a restricted feeding schedule.
Increased physical activity and decreased motivation to eat are common features in anorexia nervosa. We investigated the development of these features and the potential implication of brain-derived neurotrophic factor (BDNF) and dopaminergic signalling in their development in C57BL/6J and A/J inbred mice, using the 'activity-based anorexia' model. In this model, mice on a restricted-feeding schedule are given unlimited access to running wheels. We measured dopamine receptor D2 and BDNF expression levels in the caudate putamen and the hippocampus, respectively, using in situ hybridization. We found that in response to scheduled feeding, C57BL/6J mice reduced their running wheel activity and displayed food anticipatory activity prior to food intake from day 2 of scheduled feeding as an indication of motivation to eat. In contrast, A/J mice increased running wheel activity during scheduled feeding and lacked food anticipatory activity. These were accompanied by increased dopamine receptor D2 expression in the caudate putamen and reduced BDNF expression in the hippocampus. Consistent with human linkage and association studies on BDNF and dopamine receptor D2 in anorexia nervosa, our study shows that dopaminergic and BDNF signalling are altered as a function of susceptibility to activity-based anorexia. Differences in gene expression and behaviour between A/J and C57BL/6J mice indicate that mouse genetic mapping populations based on these progenitor lines are valuable for identifying molecular determinants of anorexia-related traits.
Gelegen
C
C
Rudolf Magnus Institute of Neuroscience, Department of Neuroscience and Pharmacology, Behavioural Genomics Section, University Medical Centre Utrecht, Utrecht, The Netherlands.
van den Heuvel
J
J
Collier
D A
DA
Campbell
I C
IC
Oppelaar
H
H
Hessel
E
E
Kas
M J H
MJ
D000818:Animals; D000856:Anorexia Nervosa / Q000235:genetics* / Q000378:metabolism; D019208:Brain-Derived Neurotrophic Factor / Q000235:genetics* / Q000378:metabolism*; D031204:Caloric Restriction; D004195:Disease Models, Animal; D005260:Female; D006624:Hippocampus / Q000502:physiology; D017403:In Situ Hybridization; D051379:Mice; D008805:Mice, Inbred A; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009043:Motor Activity / Q000502:physiology; D017072:Neostriatum / Q000502:physiology; D010805:Physical Conditioning, Animal; D012333:RNA, Messenger / Q000378:metabolism; D017448:Receptors, Dopamine D2 / Q000235:genetics* / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology; D013045:Species Specificity
D019208:Brain-Derived Neurotrophic Factor; D012333:RNA, Messenger; D017448:Receptors, Dopamine D2