63 4 Journal of Molecular D Aguinaga et al. Cocaine, ghrelin, sigma-1 63:4 R81–R92 Endocrinology receptors, and appetite REVIEW The sigma-1 receptor as key common factor in cocaine and food-seeking behaviors David Aguinaga1,2, Mireia Casanovas1,2, Rafael Rivas-Santisteban1,2, Irene Reyes-Resina1,2,†, Gemma Navarro2,3 and Rafael Franco1,2 1Department of Biochemistry and Molecular Biomedicine, School of Biology, Universitat de Barcelona, Barcelona, Spain 2Centro de Investigación en Red, Enfermedades Neurodegenerativas, CiberNed, Instituto de Salud Carlos III, Madrid, Spain 3Department of Biochemistry and Physiology, School of Pharmacy and Food Sciences, Universitat de Barcelona, Barcelona, Spain Correspondence should be addressed to R Franco or G Navarro:
[email protected] or
[email protected] †(I Reyes-Resina is now at Research Group Neuroplasticity, Leibniz Institute for Neurobiology, Magdeburg, Germany) Abstract Addiction and eating disorders involve brain reward circuits. Binge eating predisposes Key Words to addictive behavior, while the cessation of exposure to drugs of abuse leads to reward f Dopamine receptors activities, including intake of tasty foods. Cocaine use is associated with a decrease in f Ghrelin receptors food intake, with reversal after drug use is discontinued. Exciting new findings show that f Orexin receptors receptors for the ‘hunger’ hormone, ghrelin, directly interact with the sigma-1 receptor f MAP kinase (σ1R), which is a target of cocaine. σ1Rs are key players in regulating dopaminergic f Receptor heteromers neurotransmission and ghrelin-mediated actions. This review focuses on the σ1 receptor f Drug addiction as a general neuroendocrine regulator by directly interacting with neuronal G-protein- f Reward circuits of the CNS coupled receptors.