Investigation of Low Dose Naltrexol (LD-6BN) for the Treatment of Opioid Drug-Taking, Hyperaigesia, and Dependence

Investigation of Low Dose 6?-Naltrexol (LD-6BN) for the Treatment of Opioid Drug-Taking, Hyperalgesia, and Dependence

Hypothesis: 6?-Naltrexol at low doses (LD-6BN) binds to the µ-opioid receptor (MOR-µ) with low receptor occupancy (-10% or less), thereby not substantially affecting agonist signaling. while staying at the receptor sites with a long half-life and slowly reversing elevated ligand-free µOR (MOR-µ*) signaling. We hypothesize this pharmacological profile will reduce opioid drug-taking behavior, hyperalgesia. and dependence. Data from the previous SRA inform the revised dosing regimen for the current proposal.

Overview: Male, Sprague-Dawley rats (n=40) will be trained to self-administer intravenous oxycodone (0.1 mg/kg/infusion) until stability criteria are met (<5% in infusions earned across a minimum of three training sessions). We will then evaluate a dose response curve of compound LD-6BN to determine its efficacy to reduce opioid self-administration in a between-subjects design for five days. At 24hr after the final self ­administration session, the impact of LD-6BN on hyperalgesia and withdrawal behaviors (dependence) will be assessed.