D-cycloserine is not susceptible to self-administration using an intravenous self-administration model in male ketamine-habituated Sprague-Dawley rats.
Michael T Sapko, Taleen Hanania, Qing Chang, Jonathan C. Javitt
Pharmacology, Biochemistry, and Behavior June 2023 DOI: 10.1016/j.pbb.2023.173586 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Observational study (intravenous self-administration paradigm in rats) Peer reviewed |
|---|---|
| Population | Male adult Sprague-Dawley rats, ketamine-habituated |
| Interventions | D-cycloserine S-ketamine |
| Dose | 1.5, 5.0, and 15 mg/kg per lever press (D-cycloserine) |
| Topics | Esketamine Ketamine |
| Keywords | Abuse liability D-cycloserine Nmda receptor Self-administration |
| Key findings | D-cycloserine did not support self-administration in ketamine-dependent rats at any dose tested (1.5, 5.0, or 15 mg/kg per lever press), with self-infusion behavior similar to saline. S-ketamine substituted for ketamine and maintained self-administration at the same frequency. The authors conclude that D-cycloserine has no apparent abuse liability in this rodent model. |
Abstract
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.
Comparable studies
Other preclinical and animal studies on ketamine, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| mTOR-Dependent Synapse Formation Underlies the Rapid Antidepressant Effects of NMDA Antagonists Rats | 2010 | Observational study | |
| Activation of Glutamatergic Neurotransmission by Ketamine: A Novel Step in the Pathway from NMDA Receptor Blockade to Dopaminergic and Cognitive Disruptions Associated with the Prefrontal Cortex Conscious rats | 1997 | Dose-response study with microdialysis and behavioral testing | |
| NMDAR inhibition-independent antidepressant actions of ketamine metabolites Mice | 2016 | Preclinical study | |
| The dissociative anaesthetics, ketamine and phencyclidine, selectively reduce excitation of central mammalian neurones by N‐methyl‐aspartate Spinal neurons in decerebrate or pentobarbitone-anaesthetized cats and rats | 1983 | Experimental study | |
| R-ketamine: a rapid-onset and sustained antidepressant without psychotomimetic side effects Mice | 2015 | Experimental study |
Citations in the library
Cites 4
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- Pharmacological and behavioral divergence of ketamine enantiomers: implications for abuse liability Molecular Psychiatry April 15, 2021
- Noribogaine reduces nicotine self-administration in rats. Journal of Psychopharmacology June 1, 2015
- Dextromethorphan abuse: clinical effects and management. Journal of the American Pharmacists Association 2009