The lateral hypothalamus as integrator of metabolic and environmental needs: from electrical self-stimulation to opto-genetics.

As one of the evolutionary oldest parts of the brain, the diencephalon evolved to harmonize changing environmental conditions with the internal state for survival of the individual and the species. The pioneering work of physiologists and psychologists around the middle of the last century clearly demonstrated that the hypothalamus is crucial for the display of motivated behaviors, culminating in the discovery of electrical self-stimulation behavior and providing the first neurological hint accounting for the concepts of reinforcement and reward. Here we review recent progress in understanding the role of the lateral hypothalamic area in the control of ingestive behavior and the regulation of energy balance.

Neural systems controlling the drive to eat: mind versus metabolism.

With the bleak outlook that 75% of Americans will be overweight or obese in 10 years, it is essential to find efficient help very soon. Knowledge of the powerful and complex neural systems conferring the basic drive to eat is a prerequisite for designing efficient therapies. Recent studies suggest that the cross talk between brain areas involved in cognitive, emotional, and metabolic-regulatory functions may explain why energy homeostasis breaks down for many predisposed individuals in our modern environment.

Increased adiposity on normal diet, but decreased susceptibility to diet-induced obesity in mu-opioid receptor-deficient mice.

The mu-opioid receptor encoded by the Oprm1 gene plays a crucial role in the mediation of food reward and drug-induced positive reinforcement, but its genetic deletion has been shown to provide food intake-independent, partial protection from diet-induced obesity. We hypothesized that mu-opioid receptor-deficient mice would show an even greater, intake-dependent, resistance to high-fat diet-induced obesity if the diet comprises a sweet component. We generated an F2 population by crossing the heterozygous offspring of homozygous female Oprm1(-/-) mice (on a mixed C57BL/6 and BALB/c genetic background) with male inbred C57BL/6 mice.