Evidence for the role of the endocannabinoid system in food-seeking behavior comes from a variety of cannabinoid studies. Emerging data suggests that THC acts via CB receptors in the hypothalamic nuclei to directly increase appetite. It is thought that hypothalamic neurons tonically produce endocannabinoids that work to tightly regulate hunger. The amount of endocannabinoids produced is inversely correlated with the amount of leptin in the blood.  For example, mice without leptin not only become massively obese but express abnormally high levels of hypothalamic endocannabinoids as a compensatory mechanism.  Similarly, when these mice were treated with an endocannabinoid inverse agonists, such as rimonabant, food intake was reduced.  When the CB receptor is knocked out in mice, these animals tend to be leaner and less hungry than wild-type mice. A related study examined the effect of THC on the hedonic (pleasure) value of food and found enhanced dopamine release in the nucleus accumbens and increased pleasure-related behavior after administration of a sucrose solution.  A related study found that endocannabinoids affect taste perception in taste cells.  In taste cells, endocannabinoids were shown to selectively enhance the strength of neural signaling for sweet tastes, whereas leptin decreased the strength of this same response. While there is need for more research, these results suggest that cannabinoid activity in the hypothalamus and nucleus accumbens is related to appetitive, food-seeking behavior.