Delivering molecularly targeted therapies to specific brain regions is difficult because neurons vary in type and function. A miniaturized, implantable drug delivery system that allows real-time adjustment of treatments is described. Using this method, a drug (U-50488) that activates kappa opioid receptors was infused into the dorsal medial nucleus accumbens shell of the brain. Infusions into the dorsal region caused a reward-like conditioned place preference, while infusions just 1 mm more ventral caused conditioned place aversion. This precision may aid other neurotherapeutic interventions.
Activating kappa opioid receptors (KOR) in rats produces a biphasic effect on cocaine's rewarding properties. When cocaine was given within an hour of the KOR agonist salvinorin A, the drug's rewarding effects and dopamine release were amplified. However, when cocaine was administered 24 hours later, these effects were diminished. The study also found changes in gene expression and dopamine levels in brain reward regions at the 24-hour mark. The authors propose that KOR activation, which occurs during cocaine withdrawal, may time-dependently alter vulnerability to cocaine's effects.