Effect of chronic delivery of the NOP/MOR partial agonist AT-201 and NOP antagonist J-113397 on heroin relapse in a rat model of opioid maintenance.

Autor: Bossert JM; Behavioral Neuroscience Branch, IRP/NIDA/NIH, Baltimore, MD, U.S.A.. jennifer.bossert@nih.gov., Caldwell KE; Behavioral Neuroscience Branch, IRP/NIDA/NIH, Baltimore, MD, U.S.A., Korah H; Behavioral Neuroscience Branch, IRP/NIDA/NIH, Baltimore, MD, U.S.A., Batista A; Behavioral Neuroscience Branch, IRP/NIDA/NIH, Baltimore, MD, U.S.A., Bonbrest H; Behavioral Neuroscience Branch, IRP/NIDA/NIH, Baltimore, MD, U.S.A., Fredriksson I; Behavioral Neuroscience Branch, IRP/NIDA/NIH, Baltimore, MD, U.S.A., Jackson SN; Translational Analytical Core, IRP/NIDA/NIH, Baltimore, MD, U.S.A., Sulima A; Molecular Targets and Medications Discovery Branch, IRP/NIDA, NIAAA/NIH, Baltimore, MD, U.S.A., Rice KC; Molecular Targets and Medications Discovery Branch, IRP/NIDA, NIAAA/NIH, Baltimore, MD, U.S.A., Zaveri NT; Astraea Therapeutics, 320 Logue Avenue, Mountain View, CA, USA., Shaham Y; Behavioral Neuroscience Branch, IRP/NIDA/NIH, Baltimore, MD, U.S.A.
Jazyk: angličtina
Zdroj: Psychopharmacology [Psychopharmacology (Berl)] 2024 Dec; Vol. 241 (12), pp. 2497-2511. Date of Electronic Publication: 2024 Sep 13.
DOI: 10.1007/s00213-024-06678-7
Abstrakt: Rationale: The opioid crisis persists despite availability of effective opioid agonist maintenance treatments (methadone and buprenorphine). Thus, there is a need to advance novel medications for the treatment of opioid use and relapse.
Objectives: We recently modeled maintenance treatment in rats and found that chronic delivery of buprenorphine and the mu opioid receptor (MOR) partial agonist TRV130 decreases relapse to oxycodone seeking and taking. In contrast, chronic delivery of the buprenorphine analog BU08028 had mixed effects on different heroin relapse-related measures. Here, we tested the effect of the mixed nociceptin (NOP) receptor/MOR partial agonist AT-201 and the NOP receptor antagonist J-113397 on different heroin relapse-related measures.
Methods: We trained male and female rats to self-administer heroin (6-h/d, 14-d) in context A and then implanted osmotic minipumps containing AT-201 (0, 3.8, or 12 mg/kg/d) or J-113397 (0, 12.6, or 40 mg/kg/d). Next, we tested the effect of chronic delivery of the compounds on (1) incubation of heroin seeking in a non-drug context B, (2) extinction responding reinforced by heroin-associated discrete cues in context B, (3) context A-induced reinstatement of heroin seeking, and (4) reacquisition of heroin self-administration in context A.
Results: In females, AT-201 modestly increased reacquisition of heroin self-administration and J-113397 modestly decreased incubation of heroin seeking. The compounds had no effect on the other relapse-related measures in females, and no effect on any of the measures in males.
Conclusion: The NOP/MOR partial agonist AT-201 and the NOP antagonist J-113397 did not mimic buprenorphine's inhibitory effects on relapse in a rat model of opioid maintenance treatment.
Competing Interests: Declarations Conflict of interest The authors declare no conflicts of interest.
(© 2024. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)
Databáze: MEDLINE
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