Samenvatting

From the thesis:
"Summary
Metabolic diseases that are characterized by a disturbance in energy balance because of feeding behavior, such as obesity and anorexia are known to be a world-wide problem. A better understanding in central regulation of energy intake and metabolism could give more insight in options for treatment. Because feeding behavior is crucial for survival, motivation is expected to have an important influence. The dopaminergic (DA) system is known to be important in motivational behavior with a projection from the Ventral Tegmental Area (VTA) to the Nucleus Accumbens (NAc). The DA system is also known to have an influence on somatic activity and therefore energy expenditure. The exact role of the DA in feeding behavior and metabolism is yet to be discovered. Hyperdopaminergic mutant mice were proven to be hyperactive (increased energy expenditure) and hyperphagic compared with wild-type littermates. Dopamine-deficient mice were found to be hypoactive and hypophagic, which caused a negative energy balance unless they were treated with L-DOPA (a precursor of DA). Psychoactive drugs (such as amphetamine and cocaine) are known to increase the availability of DA and thereby locomotor activity. This effect was abolished by specific dopaminergic (6-ODHA) lesions in the VTA and the NAc. Feeding hormones have been found to have a binding spot on the VTA dopaminergic cells. Direct infusion of leptin into the VTA caused a decrease in DA firing rate in the NAc and a decrease in food intake. Ghrelin, a hunger stimulating peptide, caused an increase in DA firing rate, locomotion and food intake. These results suggest a positive influence of the VTA on food intake and energy expenditure. However, psychoactive drugs and hormones could be unspecific to DA neurons and (partial) lesions could either interfere with other processes or could cause adaption of signaling pathways for compensation."