Suppression of Methamphetamine Self-Administration by Ketamine Pre-treatment Is Absent in the Methylazoxymethanol (MAM) Rat Model of Schizophrenia
Jana Ruda-Kucerova, Zuzana Babinska, Tibor Stark, Vincenzo Micale
Neurotoxicity Research July 1, 2017 DOI: 10.1007/s12640-017-9718-9 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Controlled laboratory experiment Peer reviewed |
|---|---|
| Population | Male Sprague-Dawley rats (MAM-treated and control) |
| Intervention | Ketamine |
| Dose | 5 mg/kg |
| Topics | Ketamine Esketamine |
| Keywords | Mam model Methamphetamine Self-administration Sprague-dawley rats |
| Citations | 26 |
| Key findings | Ketamine (5 mg/kg) significantly reduced methamphetamine intake in control rats but not in MAM-treated rats, indicating a differential effect in the schizophrenia model. |
Abstract
Ketamine may prove to be a potential candidate in treating the widespread drug addiction/substance abuse epidemic among patients with schizophrenia. Clinical studies have shown ketamine to reduce cocaine and heroin cravings. However, the use of ketamine remains controversial as it may exacerbate the symptoms of schizophrenia. Therefore, the aim of this study is to characterize the effects of ketamine on drug addiction in schizophrenia using the methylazoxymethanol (MAM) acetate rat model on operant IV methamphetamine (METH) self-administration. MAM was administered intraperitoneally (22 mg/kg) on gestational day 17. Locomotor activity test and later IV self-administration (IVSA) were then performed in the male offspring followed by a period of forced abstinence and relapse of METH taking. After reaching stable intakes in the relapse phase, ketamine (5 mg/kg) was administered intraperitoneally 30 min prior to the self-administration session. As documented previously, the MAM rats showed a lack of habituation in the locomotor activity test but developed stable maintenance of METH self-administration with no difference in operant behaviour to control animals. Results show that ketamine treatment significantly reduced the METH intake in the control animals but not in MAM animals. Ketamine effect on METH self-administration may be explained by increased glutamatergic signalling in the prefrontal cortex caused by the N-methyl-D-aspartate antagonism and disinhibition of GABA interneurons which was shown to be impaired in the MAM rats. This mechanism may at least partly explain the clinically proven anti-craving potential of ketamine and allow development of more specific anti-craving medications with fewer risks.
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
Cited by 4
- The Effects of Peripubertal THC Exposure in Neurodevelopmental Rat Models of Psychopathology International Journal of Molecular Sciences February 15, 2023
- Ketamine's Therapeutic Role in Substance Use Disorders: A Narrative Review. NeuroSci August 27, 2025
- Phytocannabinoids and schizophrenia: Focus on adolescence as a critical window of enhanced vulnerability and opportunity for treatment. Pharmacological Research December 1, 2021
- Crosstalk between the transcriptional regulation of dopamine D2 and cannabinoid CB1 receptors in schizophrenia: Analyses in patients and in perinatal Δ9-tetrahydrocannabinol-exposed rats. Pharmacological Research February 2021
Cites 13
- BDNF Release Is Required for the Behavioral Actions of Ketamine The International Journal of Neuropsychopharmacology October 31, 2014
- Ketamine psychotherapy for heroin addiction: immediate effects and two-year follow-up. Journal of Substance Abuse Treatment December 1, 2002
- KETAMINE'S MECHANISM OF ACTION: A PATH TO RAPID‐ACTING ANTIDEPRESSANTS Depression and Anxiety April 6, 2016
- Therapeutic infusions of ketamine: Do the psychoactive effects matter? Drug and Alcohol Dependence January 15, 2014
- Antidepressant mechanism of ketamine: perspective from preclinical studies Frontiers in Neuroscience July 21, 2015
and 8 more in the library