D-cycloserine is not susceptible to self-administration using an intravenous self-administration model in male ketamine-habituated Sprague-Dawley rats

• Published in: Pharmacology, biochemistry and behavior biochemistry and behavior, 2023-06, Vol.227-228, p.173586-173586, Article 173586
• Main Authors: Sapko, Michael T., Hanania, Taleen, Chang, Qing, Javitt, Jonathan C.
• Format: Article
• Language: English
• Subjects: Abuse liability; D-cycloserine; Esketamine; Ketamine; NMDA receptor; Self-administration
• ISSN: 0091-3057; 1873-5177
• DOI: 10.1016/j.pbb.2023.173586

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 for its efficacy in substituting for ketamine in ketamine-dependent rats. A standard intravenous self-administration study was conducted in male adult Sprague-Dawley rats to study 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 the intravenous drug administration apparatus. DCS was provided for self-infusion by test subjects at doses of 1.5, 5.0, and 15 mg/kg per lever press. 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 self-administration at any of the test doses. The self-infusion behavior of DCS was similar to control (saline). D-cycloserine, a partial agonist 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.