Meta-analysis of pre-clinical studies on the effects of opioid receptor ligands on food intake, motivation, and choice

The opioid receptors (OR) regulate food intake. Still, despite extensive pre-clinical research, the overall effects and individual contribution of the mu (MOR), kappa (KOR), and delta (DOR) OR subtypes to feeding behaviors and food intake remain unclear. To address this, we conducted a pre-registered systematic search and meta-analysis of rodent dose-response studies to evaluate the impact of central and peripheral administration of non-selective and selective OR ligands on intake, motivation, and choice of food. All studies had a high bias risk. Still, the meta-analysis confirmed the overall orexigenic and anorexigenic effects of OR agonists and antagonists, respectively. Our results support a larger orexigenic role for central MOR agonists among OR subtypes and that peripheral OR antagonists reduce motivation for and intake of preferred foods. In binary food choice studies, peripheral OR agonists selectively increase the intake of fat-preferred foods; in contrast, they did not increase the intake of sweet carbohydrate-preferred foods. Overall, these data support that OR regulation of intake, motivation, and choice is influenced by food macronutrient composition.