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) via bioRxiv
Summary
AI-generated from the abstractKetamine reduces methamphetamine-seeking behaviors and negative affect in a rat model. Methamphetamine increases glutamate release, activating NMDARs, while ketamine blocks these receptors and promotes synaptogenesis. Rats treated with ketamine showed decreased drug-seeking and withdrawal-related anxiety, suggesting a potential therapeutic role for ketamine in methamphetamine addiction.
Study at a glance
| Characteristics | Animal study |
|---|---|
| Population | Rats |
| Intervention | Ketamine |
| Topics | Addiction Anxiety Ketamine |
| Keywords | Crystal meth dependence Stimulant use disorder Methamphetamine Recovery Drug-seeking behaviors |
| Key finding | 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.