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D-cycloserine (DCS) is Not Susceptible to Self-administration, unlike S-ketamine Using an Intravenous Self-administration Model in Naive and Ketamine-habituated Sprague-Dawley Rats

Daniel C. Javitt, Jonathan C. Javitt

bioRxiv Preprint Server August 12, 2022 preprint DOI: 10.1101/2022.08.12.503713 via bioRxiv

Summary

D-cycloserine (DCS) did not substitute for ketamine in ketamine-dependent rats, suggesting low abuse potential. The study used a self-administration paradigm to evaluate whether DCS would be self-administered by rats trained to self-administer ketamine. DCS failed to maintain ketamine-reinforced behavior, indicating it lacks the reinforcing properties associated with abuse liability. This finding contrasts with NMDAR antagonist antidepressants, which have known potential for abuse. The results suggest DCS may have a lower risk of addiction compared to other drugs in its class.

Study at a glance

Characteristics Preclinical study
Population Ketamine-dependent rats
Interventions D-cycloserine ketamine
Topics Addiction
Keywords D-cycloserine Dcs Low abuse potential Non-addictive Addiction risk
Key finding D-cycloserine did not substitute for ketamine in a self-administration paradigm, indicating low abuse potential.

Abstract

OBJECTIVE N-methyl D-aspartate Receptor (NMDAR) antagonist antidepressants have known potential for abuse liability. The aim of this study was to evaluate the abuse liability of D-cycloserine (DCS), using a self-administration paradigm in which DCS was tested in its efficacy in substituting for ketamine in ketamine-dependent rats.

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