Long-lasting effects of repeated ketamine administration in adult and adolescent rats.
M L Shawn Bates, Keith A Trujillo
Behavioural Brain Research September 2, 2019 DOI: 10.1016/j.bbr.2019.111928 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Experimental study Peer reviewed |
|---|---|
| Population | Adolescent and adult male rats |
| Intervention | Ketamine |
| Dose | 25 mg/kg |
| Duration | 10-day injection period, 20-day abstinence period |
| Topics | Addiction Ketamine Esketamine |
| Keywords | Adolescence Cognition Locomotor Sensitization |
| Key findings | Repeated ketamine exposure produces long-lasting locomotor sensitization in adult but not adolescent rats, and no statistically significant cognitive deficits were observed in either age group. |
Abstract
Initiation of ketamine use often occurs in adolescence, yet little is known about long-term consequences when use begins in this developmental period. The current experiments were designed to examine the effects of repeated exposure to ketamine in adolescence on behavior in adulthood. We examined locomotor activity, as well as cognitive function, in animals that received repeated administration of ketamine. Groups of adolescent and adult male rats were treated with ketamine (25 mg/kg) once daily for 10 days. Locomotor activity was assessed following the first injection, following 10 days of injection, and following 20 days of abstinence. Acute locomotor effects and locomotor sensitization were compared in adolescents and adults; cross-sensitization to dextromethorphan, another dissociative with abusive potential, was also examined. In a separate group of animals cognitive deficits were assessed following the 20 day abstinence period in spatial learning and novel object recognition tasks. The locomotor stimulant effect of ketamine was much greater in adolescents than adults. Animals that were repeatedly administered ketamine demonstrated locomotor sensitization immediately after the final injection. However, sensitization only persisted after the abstinence period in animals treated as adults. No cross-sensitization to dextromethorphan was evident. Ketamine failed to produce statistically significant cognitive deficits in either age group, although drug-treated adults showed a trend towards deficits in spatial learning. Repeated use of ketamine produces long-lasting neuroadaptations that may contribute to addiction. Mild lasting memory deficits may occur in adults, although further work is necessary to confirm these findings. The results extend the understanding of potential long-term consequences of ketamine use in adolescents and adults.
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 |
Citations in the library
Cited by 17
- The abuse liability of ketamine: A scoping review of preclinical and clinical studies. Journal of Psychiatric Research May 1, 2022
- Ketamine and its metabolites: Potential as novel treatments for depression. Neuropharmacology October 1, 2022
- Use and abuse of dissociative and psychedelic drugs in adolescence Pharmacology, Biochemistry, and Behavior January 27, 2021
- Novel rapid treatment options for adolescent depression. Pharmacological Research March 1, 2024
- Ketamine for Depression, but at What Cost? A Review of Ketamine’s Neurotoxic Effects From Preclinical and Human Studies American Journal of Psychiatry September 10, 2025
and 12 more in the library
Cites 17
- A Randomized Trial of an N-methyl-D-aspartate Antagonist in Treatment-Resistant Major Depression Archives of General Psychiatry August 1, 2006
- Ketamine – More mechanisms of action than just NMDA blockade Trends in Anaesthesia and Critical Care March 22, 2014
- A Review of the Nonmedical Use of Ketamine: Use, Users and Consequences Journal of Psychoactive Drugs December 1, 2000
- Short‐ and long‐term antidepressant effects of ketamine in a rat chronic unpredictable stress model Brain and Behavior June 23, 2017
- Age dependence of the rapid antidepressant and synaptic effects of acute NMDA receptor blockade Frontiers in Molecular Neuroscience September 11, 2015
and 12 more in the library