GLP-1 Influences Food and Drug Reward

Natural rewards, including food, water, sleep and social interactions, are required to sustain life. The neural substrates that regulate the reinforcing effects of these behaviors are also the same neurobiological mechanisms mediating mood, motivation and the rewarding effects of pharmacological stimuli. That the neuropeptide glucagon-like peptide-1 (GLP-1) is under investigation for both the homeostatic and hedonic controls of feeding is not surprising or novel. However, if the neural substrates that underline food reward are shared with other reward-related behaviors generally, then future research should investigate and embrace the likelihood that endogenous and exogenous GLP-1 receptor activation may influence multiple reward-related behaviors. Indeed, studies of the neurobiological mechanisms underlying motivated feeding behavior have informed much of the basic research investigating neural substrates of drug addiction. An emerging literature demonstrates a role for the GLP-1 system in modulating maladaptive reward behaviors, including drug and alcohol consumption. Thus, if GLP-1-based pharmacotherapies are to be used to treat drug addiction and other diseases associated with maladaptive reward behaviors (e.g. obesity and eating disorders), the neuroscience field must conduct systematic, mechanistic neuropharmacological and behavioral studies of each GLP-1 receptor-expressing nucleus within the brain. It is possible that behavioral selectivity may result from these studies, which could inform future approaches to targeting GLP-1R signaling in discrete brain nuclei to treat motivated behaviors. Equally as likely, non-selective effects on natural reward and maladaptive reward behaviors may be observed for GLP-1-based pharmacotherapies. In this case, a better understanding of the effects of increased central GLP-1R activation on motivated behaviors will aid in clinical approaches toward treating aberrant feeding behaviors and/or drug dependence.