Recent studies suggest that spontaneous physical activity (SPA) may be under the 
non-conscious control of neuroendocrine circuits that are known to control food 
intake. To further elucidate endocrine gut-brain communication as a component of 
such circuitry, we here analyzed long-term and acute effects of the 
gastrointestinal hormones ghrelin and PYY 3-36 as well as their hypothalamic 
neuropeptide targets NPY, AgRP and POMC (alpha-MSH), on locomotor activity and 
home cage behaviors in rats. For the analysis of SPA, we used an automated 
infrared beam break activity measuring system, combined with a novel automated 
video-based behavior analysis system (HomeCageScan (HCS)). Chronic (one-month) 
peripheral infusion of ghrelin potently increased body weight and fat mass in 
rats. Such positive energy balance was intriguingly not due to an overall 
increased caloric ingestion, but was predominantly associated with a decrease in 
SPA. Chronic intracerebroventricular infusion (7 days) of ghrelin corroborated 
the decrease in SPA and suggested a centrally mediated mechanism. Central 
administration of AgRP and NPY increased food intake as expected. AgRP 
administration led to a delayed decrease in SPA, while NPY acutely (but 
transiently) increased SPA. Behavioral dissection using HCS corroborated the 
observed acute and transient increases of food intake and SPA by central NPY 
infusion. Acute central administration of alpha-MSH rapidly decreased food 
intake but did not change SPA. Central administration of the NPY receptor 
agonist PYY 3-36 transiently increased SPA. Our data suggest that the control of 
spontaneous physical activity by gut hormones or their neuropeptide targets may 
represent an important mechanistic component of energy balance regulation.