Grant: Project Grant

Prescription painkiller addiction is epidemic in Canada. Addiction is caused, in part, by powerful and long lasting memories of the drug experience. All drugs of abuse can strengthen excitatory connections onto dopamine neurons, a process that is thought to tag the associations between drug-related cues and the euphoric feeling with heightened importance. Our earlier work showed that by blocking the actions of the neuropeptide orexin, one can inhibit the drug-induced plasticity. Orexin is released in concert with dynorphin, another peptide with opposing actions on dopamine neurons. One possibility is that orexin opposes dynorphin's anti-reward properties. However, we have recently discovered that orexin and dynorphin act on different dopamine neurons that ultimately make projections to different brain regions. We will determine how these peptides modulate these different projections, and how the projections contribute to morphine seeking.