Beneficial effects of Esketamine on Morphine preference reacquisition in male rats.

Repeated or daily doses of esketamine, the S-isomer of ketamine, prevented the reestablishment of morphine-conditioned place preference in rats, suggesting it may reduce relapse risk in opioid addiction. Rats received esketamine either every five days (acute) or daily (sub-chronic) during the extinction phase of morphine conditioning. After ten days, re-exposure to morphine did not reinstate the conditioned preference in either esketamine group. This is the first experimental evidence that esketamine could be a promising treatment for opioid use disorder, though clinical studies in humans are needed.

Study at a glance

Abstract

Addiction is a chronic condition that poses a serious public health challenge, particularly highlighted by the global opioid crisis involving drugs such as morphine (MORPH). One of the major obstacles in effective detoxification is the high relapse rate, with many individuals resuming drug use after withdrawal. Pharmacological treatments developed so far have generally shown limited efficacy in addressing substance use disorder. In this context, esketamine (ESK), the S-ketamine isomer, has been used in cases of treatment-resistant recurrent depression and depression with suicide risk. In our study, rats were treated with two doses of ESK every five days (acute - A-ESK) or daily (sub-chronic - SC-ESK) during MORPH-conditioned place preference (CPP) extinction. After 10 days, the animals were re-exposed to MORPH to assess preference reacquisition in the CPP paradigm. Our findings showed that both acute and sub-chronic ESK (A-ESK and SC-ESK) effectively prevented MORPH-CPP reestablishment. To our knowledge, this is the first experimental study to demonstrate the potential of ESK as a promising treatment for opioid abuse disorder. Clinical studies are needed to confirm its efficacy in human rehabilitation centers.