A single, extinction-based treatment with a kappa opioid receptor agonist elicits a long-term reduction in cocaine relapse

Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology
Jasper A HeinsbroekJamie Peters

Abstract

Kappa opioid receptor (KOR) agonists have known anti-addiction properties and can reduce drug seeking. Their potential for clinical use has largely been daunted by their aversive properties mediated through p38 MAPK signaling. Here we examined the therapeutic potential of the KOR agonist U50,488 (U50) to reduce cocaine seeking in a self-administration model. Following cocaine self-administration and 7 days of forced home-cage abstinence, rats were administered a single dose of U50 (5 mg/kg, i.p.) 30 min prior to the first extinction training session, wherein cocaine and the discrete cocaine-paired cues were no longer available. U50 reduced cocaine seeking on this first extinction session, but did not alter extinction training over subsequent days. 2 weeks after U50 treatment, rats underwent a test of cue-induced reinstatement, and rats that had received U50 reinstated less than controls. Central inhibition of p38 MAPK at the time of U50 administration prevented its long-term therapeutic effect on reinstatement, but not its acute reduction in drug seeking on extinction day 1. The long-term therapeutic effect of U50 required operant extinction during U50 exposure, extended to cocaine-primed reinstatement, and was not mimicked by ...Continue Reading

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Citations

Oct 6, 2020·Frontiers in Molecular Neuroscience·Prita R AsihArne Ittner
Jun 24, 2020·Peptides·Richard J Bodnar
May 28, 2021·Expert Opinion on Pharmacotherapy·Gustavo A AngaritaMarc N Potenza

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BETA
light microscopy
sedation

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