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bioRxiv · 10.1101/2022.08.12.503713

D-cycloserine, a mixed NMDAR agonist/antagonist is Not Susceptible to Self-administration, unlike S-ketamine Using an Intravenous Self-administration Model in Naive and Ketamine-habituated Sprague-Dawley Rats

Javitt, D. C.·Javitt, J. C.
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Abstract

OBJECTIVEN-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. METHODSA 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. RESULTSS-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. CONCLUSIONC-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.

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Javitt, D. C., Javitt, J. C.. 2022-08-15. D-cycloserine, a mixed NMDAR agonist/antagonist is Not Susceptible to Self-administration, unlike S-ketamine Using an Intravenous Self-administration Model in Naive and Ketamine-habituated Sprague-Dawley Rats. https://doi.org/10.1101/2022.08.12.503713

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