Behavioral effects of ketamine and toxic interactions with psychostimulants

Hayase, Tamaki; Yamamoto, Yoshiko; Yamamoto, Keiichi

doi:10.1186/1471-2202-7-25

Cited by 59 publications

(17 citation statements)

References 51 publications

(57 reference statements)

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“…New psychoactive substances are available in various formulations and are mainly used as legal substitutes for traditional drugs of abuse. One of the largest and most important groups are psychostimulants, which affect a range of behavioral patterns in humans ( 1 ) and laboratory animal models ( 2 , 3 ). It has been demonstrated that the repeated administration of psychostimulants to rodents ( 2 , 4 – 8 ) and humans ( 9 ) can lead to addiction, induce changes in emotional states such as fear, anxiety, and depression, interfere with social behavior, and cause cognitive impairment.…”

Section: Introductionmentioning

confidence: 99%

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

et al. 2017

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3,4-Methylenedioxymethamphetamine (MDMA) and its derivatives, 2,5-dimethoxy-4-bromo-amphetamine hydrobromide (DOB) and para-methoxyamphetamine (PMA), are recreational drugs whose pharmacological effects have recently been attributed to serotonin 5HT2A/C receptors. However, there is growing evidence that the oxytocin (OT)/vasopressin system can modulate some the effects of MDMA. In this study, MDMA (2.5–10 mg/kg), DOB (0.5 mg/kg), or PMA (0.005, 0.1, or 0.25 mg/kg) were administered intramuscularly to adult zebra fish, alone or in combination with the V1a vasopressin antagonist, SR49059 (0.01–1 ng/kg), before carrying out conditioned place preference (CPP), social preference, novel tank diving, and light–dark tests in order to evaluate subsequent rewarding, social, and emotional-like behavior. The combination of SR49059 and each drug progressively blocked: (1) rewarding behavior as measured by CPP in terms of time spent in drug-paired compartment; (2) prosocial effects measured on the basis of the time spent in the proximity of a nacre fish picture; and (3) anxiolytic effects in terms of the time spent in the upper half of the novel tank and in the white compartment of the tank used for the light–dark test. Antagonism was obtained at SR49059 doses which, when given alone, did not change motor function. In comparison with a control group, receiving vehicle alone, there was a three to five times increase in the brain release of isotocin (the analog of OT in fish) after treatment with the most active doses of MDMA (10 mg/kg), DOB (0.5 mg/kg), and PMA (0.1 mg/kg) as evaluated by means of bioanalytical reversed-phase high-performance liquid chromatography. Taken together, these findings show that the OT/vasopressin system is involved in the rewarding, prosocial, and anxiolytic effects of MDMA, DOB, and PMA in zebra fish and underline the association between this system and the behavioral alterations associated with disorders related to substance abuse.

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Section: Introductionmentioning

confidence: 99%

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

et al. 2017

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“…Furthermore, animal data regarding the impact of ketamine on anxiety behaviors are contradictory: in a study conducted by Silvestre et al, 45 ketamine was found to produce anxiogenic-like effects in rats, but in another study, the drug was shown to promote anxiolytic responses (in the elevated plus maze). 46 Similarly, the evidence for an anxiolytic-like effect of ketamine in humans is equivocal and is probably subject to complex dose-and-time effects. For instance, in a study of healthy human volunteers, the participants reported a decrease in anxiety after a low dose of ketamine (0.1 mg/kg intravenously), but an increase in anxiety at a higher dose (0.5 mg/kg intravenously).…”

Section: Discussionmentioning

confidence: 99%

The interactive effects of ketamine and magnesium upon depressive-like pathology

Rastgar

Litteljohn

Rudyk

et al. 2016

NDT

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Approximately one-third of patients with major depressive disorders (MDDs) are resistant to current treatment methods, and the majority of cases relapse at some point during therapy. This has resulted in novel treatments being adopted, including subanesthetic doses of ketamine, which affects aberrant neuroplastic circuits, glutamatergic signaling, and the production of brain-derived neurotrophic factor. Ketamine rapidly relieves depressive symptoms in treatment-resistant major depressive disorder patients with effects that last for up to 2 weeks even after a single administration. However, it is also a drug with an abusive potential and can have marked side effects. Hence, this study aimed at enhancing the antidepressant-like effects of ketamine (allowing for lower dosing regimens) by coadministering magnesium hydroaspartate (Mg2+ normally affects the same receptors as ketamine) and also assessed whether an Mg2+-deficient diet would modify the impact of ketamine. It was found that a single 15 mg/kg dose of ketamine did indeed induce rapid antidepressant-like effects in the forced swim test but did not affect brain levels of the brain-derived neurotrophic factor. Contrary to our hypothesis, magnesium administration or deficiency did not influence the impact of ketamine on these outcomes. Thus, these data do not support the use of magnesium as an adjunct agent and instead suggest that further research involving other antidepressant and animal models is required to confirm the present findings.

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“…The lack of ketamine effects on the ETM rats performance, acutely or 24 h after its administration, reinforces the controversial findings reported in previous studies, as described in table 1. For example, anesthetic doses of ketamine induced anxiolytic-like (Hayase et al, 2006), anxiogenic-like (Morena et al, 2017) or no effect (Magalhaes et al, 2017) in different tests of anxiety. Regarding sub-anesthetic doses of ketamine, similar mix of outcomes has been previously reported (as detailed in Table 1).…”

Section: New Findingsmentioning

confidence: 99%

“…For instance, the genetic background of a strain is among the several factors that may affect the behavioral responses of the animals to a drug Võikar et al, 2001). Ketamine 30 mg/kg produced an anxiolytic-like effect on male ICR mice (Hayase et al, 2006) and no effect on male 129S6/SvEvTac mice (Brachman et al, 2016) submitted to the EPM. Ketamine 10 mg/kg induced an anxiolytic-like effect in NSF, but did not alter the behavior in the EPM and in the context and cued fear conditioning (Autry et al, 2011).…”

Section: New Findingsmentioning

confidence: 99%

Ketamine effects on anxiety and fear-related behaviors: current literature evidence and new findings

Silote

Oliveira

Ribeiro

et al. 2019

Preprint

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Highlights  Ketamine induces mixed effects in animal anxiety tests  Few studies investigated the individual effects of S-ketamine in anxiety/fear tests  None study evaluated the effects of R-Ketamine on anxiety/fear-related behaviors  Systemic ketamine does not affect panic-like behaviors in the elevated T-maze Abstract Ketamine, a non-competitive N-methyl-D-aspartate (NMDA) receptor antagonist, presents rapid and sustained antidepressant effect in clinical and preclinical studies.Regarding ketamine effects on anxiety, there is a widespread discordance among preclinical studies. To address this issue, the present study reviewed the literature (electronic database MEDLINE) to summarize the profile of ketamine effects in animal tests of anxiety/fear. We found that ketamine anxiety/fear-related effects may depend on the anxiety paradigm, schedule of ketamine administration and tested species.Moreover, there was no report of ketamine effects in animal tests of fear related to panic disorder (PD). Based on that finding, we evaluated if treatment with ketamine and another NMDA antagonist, MK-801, would induce acute and sustained (24 hours later) anxiolytic and/or panicolytic-like effects in animals exposed to the elevated T-maze (ETM). The ETM evaluates, in the same animal, conflict-evoked and fear behaviors, which are related, respectively, to generalized anxiety disorder and PD. Male Wistar rats were systemically treated with racemic ketamine (10, 30 and 80 mg/kg) or MK-801 (0.05 and 0.1 mg/kg) and tested in the ETM in the same day or 24 hours after their administration. Ketamine did not affect the behavioral tasks performed in the ETM acutely or 24 h later. MK-801 impaired inhibitory avoidance in the ETM only at 45 min post-injection, suggesting a rapid but not sustained anxiolytic-like effect. Altogether our results suggest that ketamine might have mixed effects in anxiety tests while it does not affect panic-related behaviors.

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Behavioral effects of ketamine and toxic interactions with psychostimulants

Cited by 59 publications

References 51 publications

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

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

The interactive effects of ketamine and magnesium upon depressive-like pathology

Ketamine effects on anxiety and fear-related behaviors: current literature evidence and new findings

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