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.
METHODS A standard Intravenous self-administration study was conducted in Male adult Sprague-Dawley rats. model to study compounds’ abuse liability. Potential for self-administration was assessed in ketamine-habituated subjects. Subjects were trained to press a lever to obtain food, prior to connection of the lever to intravenous drug administration apparatus. DCS was provided for self-infusion by test subjects at doses of 1.5, 5.0, and 15mg/kg per lever press.
RESULTS S-Ketamine was seen to substitute for ketamine and to result in self-administration at the same frequency. DCS was not seen to result in any self-administration at any of the test doses. The self-infusion behavior of DCS was the same as that of saline.
CONCLUSION C-cycloserine, an a mixed agonist/antagonist of the NMDAR glycine site, which has been shown to have antidepressant and anti-suicidal properties in clinical studies has no apparent potential for abuse liability in a standard rodent self-administration model.
Competing Interest Statement
DCJ and JCJ have equity interests in NRx Pharmaceuticals, Inc. and receive compensation from NRx Pharmaceuticals, Inc.
Footnotes
Funding: Research was funded by NRx Pharmaceuticals, Inc.
Competing Interests: DCJ and JCJ own equity in NRx Pharmaceuticals and are derive compensation from NRx pharmaceuticals.