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 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Experimental study Peer reviewed |
|---|---|
| Intervention | U-50488 |
| Topics | Microdosing |
| Keywords | Behavior modification Drug delivery Micro-invasive Reward and aversion |
| Key findings | 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.
Comparable studies
Other experimental studies on microdosing, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| Microdosing Clinical Study: Pharmacokinetic, Pharmacogenomic (SLCO2B1), and Interaction (Grapefruit Juice) Profiles of Celiprolol Following the Oral Microdose and Therapeutic Dose Healthy volunteers matched for SLCO2B1 genotype | 2011 | Pharmacokinetic study | n = 30 |
| Microdosing psychedelics has no impact on cognitive function in naturalistic settings Participants during their microdosing regimen | 2023 | Observational within-subjects design | n = 17 |
| PK and PK / PD Modeling of Bcl2 Inhibitor S65487 in Patients With AML and Investigation of Nonlinearity With Microdosing Phase I/II cancer patients and healthy volunteers | 2026 | Pharmacokinetic/pharmacodynamic modeling study | |
| Technical pen-based printhead for high-precision microdosing of personalized therapies. | 2026 | Experimental study | |
| Analysis of Serotonin in Caenorhabditis Elegans Subjected to Micro-Dosing with Psilocybin| Iris Publishers Caenorhabditis elegans | 2025 | Experimental study |