Substance abuse has become a major health issue in the U.S., especially of opioids, where the number of overdose deaths has skyrocketed in recent years. While there are pharmacological treatments available for opioid abuse there are currently no pharmacological agents for treating abuse of other substances such as cocaine. We have been exploring peptidic ligands, particularly those acting at kappa opioid receptors (KOR), as potential treatments for substance abuse. A major challenge in treating drug abuse is relapse after a period of abstinence. Accordingly, we have been examining compounds in the mouse conditioned place preference (CPP) assay for their ability to prevent relapse. Stress, which causes activation of KOR via release of endogenous agonist, is a common cause of relapse that can be prevented by pretreatment with KOR antagonists. In contrast, relapse due to exposure to the abused substance can be prevented by KOR agonists. In order to reach their targets in the CNS therapeutics for drug abuse must be brain penetrant. Results will be presented for peptidic ligands, including compounds acting through other opioid receptors, that can prevent drug seeking behavior for cocaine, opioids and ethanol due to stress as well as substance exposure. These compounds prevent drug seeking behavior following systemic administration, including in many cases after oral administration, making them promising lead compounds for potential development to treat substance abuse.

Developing peptides and peptidomimetics as potential treatments for substance abuse

2019 Spring National Meeting

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