Getting ready for dinner: the role of ghrelin in food anticipatory activity

In light of the still increasing prevalence of obesity and other eating disorders it is crucial to examine what happens in our brain when we are triggered to think about food. Food anticipatory activity (FAA) consists of hyperactivity and arousal preceding a time-restricted meal and reflects the underlying appetitive mechanisms when a rodent gets ready for its meal. In this thesis, two models of FAA are described. Rats display FAA under food-restricted conditions, anticipating their daily meal (restricted feeding schedule (RFS)), but also under ad libitum conditions, anticipating a daily palatable meal (palatable feeding schedule (PFS)). Despite many years of research, the mechanisms underlying FAA are still not completely understood. We have shown that ghrelin levels were increased during FAA in rats subjected to either RFS or PFS. As already had been shown for FAA in response to a RFS, ghrelin increased and GHS-R1a antagonism reduced FAA to a palatable meal. A subpopulation of neurons within the DMH/VMH responded in a highly correlated manner to a food signalling cue and to ghrelin, thereby providing a potential anatomical substrate that could drive FAA following stimulation by ghrelin. Although local hypothalamic knockdown of GHS-R1a delayed the onset of FAA (DMH, VMH) and attenuated the amplitude of FAA (DMH), FAA could still be detected. Hence, ghrelin signalling within the DMH/VMH is not essential for the development of FAA. Nevertheless, these findings underline a modulatory role of ghrelin in the regulation of FAA in RFS and PFS models, and suggest ghrelin signalling as a potential target in the treatment of disorders such as anorexia nervosa and obesity.