Leptin action in the midbrain: From reward to stress

• The long form of leptin receptors are widely expressed in different midbrain regions.
• Leptin functions as a regulatory signal in feeding, reward and stress adaptation.
• The importance of midbrain leptin signaling is currently underestimated and deserved more attention.

The midbrain is a heterogenous brain structure that serves important roles in feeding regulation, motivation and reward, movement and stress adaptation. One common feature of different midbrain regions is that they all express the long form of leptin receptor (LepRb). Leptin is mainly produced and secreted by white adipose tissue, informing the brain centers via LepRb about the amount of fat storage in the body. In this way, leptin exerts its action in the midbrain to regulate different functions. First, this review deals with the basic information of leptin and its signaling. Then, attention is given to various interactions of leptin with the midbrain regions, including ventral tegmental area (VTA), substantia nigra pars compacta (SNc), rostral linear raphe (RLi) and centrally-projecting Edinger–Westphal nucleus (EWcp). Also, the projection areas of these midbrain regions are discussed. Finally, the possible function of leptin in the midbrain is suggested.