Microdosing of a kappa opioid receptor agonist within proximal nucleus accumbens shell microstructures revealing opposing behavioral outcomes.
Erin B Rousseau, Hannah D Jackson, Suman Guha, Sydney S Sherman, Michael Cima, Elena H Chartoff
Neuroscience December 17, 2024 DOI: 10.1016/j.neuroscience.2024.10.047 via PubMed
Summary
AI-generated from the abstractDelivering 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.
Study at a glance
| Characteristics | Experimental study Peer reviewed |
|---|---|
| Intervention | U-50488 |
| Keywords | Behavior modification Drug delivery Micro-invasive Reward and aversion |
| Key finding | Micro infusions of U-50488 into the dorsal medial nucleus accumbens shell induce reward-like conditioned place preference, whereas a 1 mm ventral shift induces conditioned place aversion. |
Abstract
Targeted intracranial delivery of molecularly-specific therapies within intricate brain structures poses a formidable challenge due to the heterogeneity of neuronal phenotypes and functions. Here we report the use of an implantable, miniaturized neural drug delivery system permitting dynamic adjustment of pharmacotherapies. Specifically, we exploit the spatial accuracy afforded by this method for targeting modulation of neuronal microstructures. Kappa opioid receptors (KOR) within the dorsal medial nucleus accumbens shell (NASh) are selectively activated through micro infusions of the KOR agonist, U-50488. Remarkably, we demonstrate that micro infusions of U-50488 into the dorsal NASh induces reward-like conditioned place preferences, whereas a mere 1 mm shift ventrally results in conditioned place aversions. The striking precision afforded by this method may prove useful in other neurotherapeutic interventions.