Behavioral effects of ketamine and toxic interactions with psychostimulants
T. Hayase, Yoshiko Yamamoto, Keiichi Yamamoto
BMC Neuroscience March 16, 2006 DOI: 10.1186/1471-2202-7-25 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Animal experimental study Peer reviewed |
|---|---|
| Population | ICR mice |
| Interventions | Ketamine Cocaine Methamphetamine |
| Dose | Ketamine 30 mg/kg or 100 mg/kg i.p.; cocaine 30 mg/kg or 70 mg/kg i.p.; methamphetamine 4 mg/kg or 15 mg/kg i.p. |
| Measures | Forced swimming test, elevated plus-maze test |
| Topics | Esketamine Ketamine |
| Key findings | Ketamine reversed cocaine- and methamphetamine-induced stress- and anxiety-related behaviors and reduced seizure severity at toxic psychostimulant doses, but co-treatment with high-dose ketamine significantly increased mortality, showing that ketamine can enhance the lethal effects of these psychostimulants. |
Abstract
BackgroundThe anesthetic drug ketamine (KT) has been reported to be an abused drug and fatal cases have been observed in polydrug users. In the present study, considering the possibility of KT-enhanced toxic effects of other drugs, and KT-induced promotion of an overdose without making the subject aware of the danger due to the attenuation of several painful subjective symptoms, the intraperitoneal (i.p.) KT-induced alterations in behaviors and toxic interactions with popular co-abused drugs, the psychostimulants cocaine (COC) and methamphetamine (MA), were examined in ICR mice.ResultsA single dose of KT caused hyperlocomotion in a low (30 mg/kg, i.p.) dose group, and hypolocomotion followed by hyperlocomotion in a high (100 mg/kg, i.p.) dose group. However, no behavioral alterations derived from enhanced stress-related depression or anxiety were observed in the forced swimming or the elevated plus-maze test. A single non-fatal dose of COC (30 mg/kg, i.p.) or MA (4 mg/kg, i.p.) caused hyperlocomotion, stress-related depression in swimming behaviors in the forced swimming test, and anxiety-related behavioral changes (preference for closed arms) in the elevated plus-maze test. For the COC (30 mg/kg) or MA (4 mg/kg) groups of mice simultaneously co-treated with KT, the psychostimulant-induced hyperlocomotion was suppressed by the high dose KT, and the psychostimulant-induced behavioral alterations in the above tests were reversed by both low and high doses of KT. For the toxic dose COC (70 mg/kg, i.p.)- or MA (15 mg/kg, i.p.)-only group, mortality and severe seizures were observed in some animals. In the toxic dose psychostimulant-KT groups, KT attenuated the severity of seizures dose-dependently. Nevertheless, the mortality rate was significantly increased by co-treatment with the high dose KT.ConclusionOur results demonstrated that, in spite of the absence of stress-related depressive and anxiety-related behavioral alterations following a single dose of KT treatment, and in spite of the KT-induced anticonvulsant effects and attenuation of stress- and anxiety-related behaviors caused by COC or MA, the lethal effects of these psychostimulants were increased by KT.
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 19
- Short‐ and long‐term antidepressant effects of ketamine in a rat chronic unpredictable stress model Brain and Behavior June 23, 2017
- Psilocin and ketamine microdosing: effects of subchronic intermittent microdoses in the elevated plus-maze in male Wistar rats Behavioural Pharmacology March 13, 2018
- Comparison of the Psychopharmacological Effects of Tiletamine and Ketamine in Rodents Neurotoxicity Research June 2, 2017
- Ketamine disrupts locomotion and electrolocation in a novel model of schizophrenia, Gnathonemus petersii fish Journal of Neuroscience Research March 3, 2023
- The Non-Peptide Arginine-Vasopressin v1a Selective Receptor Antagonist, SR49059, Blocks the Rewarding, Prosocial, and Anxiolytic Effects of 3,4-Methylenedioxymethamphetamine and Its Derivatives in Zebra Fish Frontiers in Psychiatry August 13, 2017
and 14 more in the library
Cites 3
- Patterns of recreational drug use at dance events in Edinburgh, Scotland Addiction July 1, 2001
- Iboga compounds reverse the behavioural disinhibiting and corticosterone effects of acute methamphetamine: Implications for their antiaddictive properties. Pharmacology, Biochemistry, and Behavior 2001
- Ketamine dependence. Anaesthesia and intensive care June 1, 2002