The endogenous opioid system, initially characterized over 30 years ago, is a primary example of a multifunctional neural system involved in a wide range of basic homeostatic behaviors, including pain control, sexual behavior, learning and memory, reward, addiction and motivation, immune function, thermoregulatory, cardiovascular and respiratory processes, and as this review indicates, the regulation of energy balance through the modulation of food intake. Given the complexity and breadth of both the endogenous opioid system itself and the complex nature of energy regulation, this review is designed to inform the reader of the systematic steps taken by the field as a whole to understand their interaction. Thus, this review will focus on: (a) discovery and characterization of the endogenous opioids and their receptors, (b) early evidence involving the opioid system in ingestive behavior, (c) the role of opioids in rewarding aspects of food intake, (d) the role of macronutrient choice in opioid-induced feeding, (e) the specific roles of opiate receptor subtypes and specific brain sites in regulating opioid-induced feeding, (f) molecular mechanisms governing opioid-induced feeding, and (g) interactions of opioid-induced feeding with dopamine and other orexigenic neuropeptides.
Discovery and characterization of the endogenous opioids and their receptors
The existence of an endogenous receptor in animals that bound opiates was reported in 1973 (Pert & Snyder, 1973; Simon et al., 1973; Terenius, 1973). Shortly thereafter, it became apparent that multiple subtypes (mu, delta and kappa) of the receptor existed (Martin et al., 1976; Lord et al., 1977).