The Effects of Ketamine on Methamphetamine Withdrawal-Induced Anxiety and Drug-Seeking Behaviors in the Rat
Marco German Ghilotti, Ricardo Petrilli Fortuna, Kofi Osei-Abrefa Ayensu, Danielle Stern, Ellen M. Unterwald
bioRxiv Preprint Server June 24, 2025 preprint DOI: 10.1101/2025.06.24.661345 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Animal study |
|---|---|
| Population | Rats |
| Intervention | Ketamine |
| Topics | Addiction Anxiety Ketamine Esketamine |
| Keywords | Crystal meth dependence Stimulant use disorder Methamphetamine Recovery Drug-seeking behaviors Ketamine for addiction Therapeutic Treatment Addiction withdrawal Detoxification Symptoms |
| Key points | Ketamine reduces methamphetamine-seeking behaviors and associated negative affect in a rat model. |
Abstract
Background The use of methamphetamine has continued to rise in the US. In addition to facilitating dopamine neurotransmission, methamphetamine indirectly increases glutamate release which activates N-methyl-D-aspartate receptors (NMDARs). Ketamine is a noncompetitive NMDAR antagonist. Ketamine also has actions on α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors (AMPARs) and promotes synaptogenesis. Thus, we hypothesized that ketamine may be a potential therapeutic to reduce methamphetamine-seeking behaviors and associated negative affect in a rat model.
Comparable studies
Other preclinical and animal studies on ketamine for addiction, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| R-(-)-ketamine modifies behavioral effects of morphine predicting efficacy as a novel therapy for opioid use disorder. Morphine-dependent rats and mice | 2020 | Preclinical study | |
| The effects of (2R,6R)-hydroxynorketamine on oxycodone withdrawal and reinstatement. Male and female oxycodone-dependent mice | 2023 | Preclinical study | |
| Characterizing the therapeutical use of ketamine for adolescent rats of both sexes: Antidepressant-like efficacy and safety profile. Adolescent rats of both sexes, including naïve and early-life stressed (maternal... | 2025 | Preclinical study | |
| Exploring ketamine's reinforcement, cue-induced reinstatement, and nucleus accumbens cFos activation in male and female long evans rats. Long Evans rats | 2024 | Preclinical experimental study | |
| Brain acid sphingomyelinase controls addiction-related behaviours in a sex-specific way. Male and female mice with forebrain ASM overexpression | 2025 | Experimental study |