Ketamine-enhanced immobility in forced swim test: A possible animal model for the negative symptoms of schizophrenia

Chindo, Ben A.; Adzu, Bulus; Yahaya, Tijani Adeniyi; Gamaniel, K.

doi:10.1016/j.pnpbp.2012.04.018

Cited by 65 publications

(48 citation statements)

References 76 publications

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“…Besides, accumulating evidence shows that ketamine also bind to other allosteric sites in the brain, such as phencyclidine-binding site within the NMDA receptor channel complex [40] and dopamine-D 2 receptor binding sites in the hippocampus [41]. However, the findings from Chindo et al [19] suggest that ketamine-enhanced immobility in the FST might be Evidence derived supports oxidative stress in the pathophysiology of schizophrenia [45]. In fact, accumulating body of evidences has reportedly demonstrated increase in the concentrations of oxidative stress parameters after treatment with classical antipsychotics such as, haloperidol [7] [8] [15] [46]; and that treatments with antioxidants like vitamin E lowered the levels of reactive oxygen species (ROS) and protected the cells.…”

Section: Discussionmentioning

confidence: 96%

“…Of note, a recent study elsewhere demonstrated that risperidone reduced the enhanced duration of immobility by ketamine in experimental mice comparable to paroxetine, a selective serotonine reuptake inhibitor [19]. Thus, the effect of risperidone on the negative symptoms has been positively correlated to its 5-hydroxy-tryptaminergic (5-HT) 5HT 2A receptor blocking action [20].…”

Section: Discussionmentioning

confidence: 99%

“…Ketamine-induced enhancement of immobility in forced swim test (FST) following acute and sub-chronic administrations of DOX against ketamine, has been previously used as an animal model for behavioral despair in experimental mice; which is indicative of negative symptoms (anhedonia, social withdrawal) of schizophrenia [19] [39].…”

Section: Discussionmentioning

confidence: 99%

“…Different doses of ketamine were used in this study: Single dose of ketamine (10 mg/kg, i.p.) [17] administrations was used to induce stereotypy and hyperlocomotion (positive symptoms) respectively; ketamine (30 mg/kg, i.p./day) [19] was used for enhancement of immobility time (negative symptoms) following 5 days treatment and thereafter animals were treated with single administration of doxycycline 24 hr after the last treatment with ketamine, followed by behavioral despair assessment in the forced swim test. Furthermore, catalepsy test was also employed for the assessment of cataleptic behavior (extrapyramidal side effect) ( Figure 1).…”

Section: Experimental Designmentioning

confidence: 99%

“…which is reflected as a state of despair in mice as described by Chindo et al [19] and Chatterjee et al [20], with brief modifications. The reduction in the immobility time serves as a specific and selective index of antidepressant activity that can be used to alleviate the negative symptoms of schizophrenia.…”

Section: Ketamine-enhanced Immobility In Forced Swim Testmentioning

confidence: 99%

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Doxycycline Ameliorates Schizophrenia-Like Behaviors in Experimental Models in Mice by Targeting Underlying Oxidative Stress

Ben-Azu¹,

Omogbiya²,

Aderibigbe³

et al. 2016

JBBS

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Current evidences support the inhibition of oxidative and inflammatory signaling mechanisms in the treatment of schizophrenia; as cure for this disease still remains limited. Doxycycline is a tetracycline antibiotic (a minocycline congener) with strong antioxidant and anti-inflammatory properties, and better pharmacokinetic profiles. Preclinical evidence indicates that minocycline possesses antipsychotic properties. This present study was designed to evaluate the effect of doxycycline on schizophrenialike behaviors, as well as biomarkers of oxidative stress in mice brains. Noveltyinduced rearing (NIR) behavior was used to evaluate the tranquilizing effect of doxycycline (25 -200 mg/kg). The acute antipsychotic effects of doxycycline were assessed using apomorphine-induced stereotypy, ketamine-induced stereotypy, hyperlocomotion and enhanced immobility in forced swim test (FST). Catalepsy test was also employed to evaluate the extrapyramidal adverse effect of doxycycline in mice. The chronic antipsychotic effect of doxycycline was evaluated following oral administration of doxycycline in combination with ketamine (100 mg/kg) intraperitoneally for 10 days. Twenty four hours after the last administration, positive (locomotor activity), cognitive (Y-maze) and negative (FST) symptoms were assessed. Thereafter, levels of biomarkers of oxidative stress were evaluated in mice brains. Doxycycline significantly (P < 0.05) decreased NIR, inhibited stereotypy induced by apomorphine and ketamine. Additionally, doxycycline significantly (P < 0.05) prevented ketamineinduced hyperlocomotion, cognitive deficit and reduced enhanced-immobility by ketamine in mice. Furthermore, doxycycline decreased malondialdehyde concentrations in a dose-related manner. Moreover, doxycycline significantly (P < 0.05) prevented the decrease in glutathione, and increased activities of superoxide dismutase and catalase in brain tissues. The results from this study suggest that doxycycline 540ameliorated schizophrenic-like behaviors via mechanisms related to attenuation of oxidative stress in mouse brain.

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Section: Discussionmentioning

confidence: 96%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Experimental Designmentioning

confidence: 99%

Section: Ketamine-enhanced Immobility In Forced Swim Testmentioning

confidence: 99%

See 3 more Smart Citations

Doxycycline Ameliorates Schizophrenia-Like Behaviors in Experimental Models in Mice by Targeting Underlying Oxidative Stress

Ben-Azu¹,

Omogbiya²,

Aderibigbe³

et al. 2016

JBBS

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Antipsychotic, antidepressant, and cognitive-impairment properties of antipsychotics: rat profile and implications for behavioral and psychological symptoms of dementia

Kołaczkowski

Mierzejewski

Bieńkowski

et al. 2014

Naunyn-Schmiedeberg's Arch Pharmacol

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Many dementia patients exhibit behavioral and psychological symptoms (BPSD), including psychosis and depression. Although antipsychotics are frequently prescribed off-label, they can have marked side effects. In addition, comparative preclinical studies of their effects are surprisingly scarce, and strategies for discovery of novel pharmacotherapeutics are lacking. We therefore compared eight antipsychotics in rat behavioral tests of psychosis, antidepressant-like activity, and cognitive impairment as a basis for preclinical evaluation of new drug candidates. The methods used in this study include inhibition of MK-801-induced hyperactivity, forced swim test (FST), passive avoidance (PA), spontaneous locomotor activity, and catalepsy. The drugs exhibited antipsychotic-like activity in the MK-801 test but with diverse profiles in the other models. Risperidone impaired PA performance, but with some dose separation versus its actions in the MK-801 test. In contrast, clozapine, olanzapine, lurasidone, and asenapine showed little or no dose separation in these tests. Aripiprazole did not impair PA performance but was poorly active in the MK-801 test. Diverse effects were also observed in the FST: chlorpromazine was inactive and most other drugs reduced immobility over narrow dose ranges, whereas clozapine reduced immobility over a wider dose range, overlapping with antipsychotic activity. Although the propensity of second-generation antipsychotics to produce catalepsy was lower, they all elicited pronounced sedation. Consistent with clinical data, most currently available second-generation antipsychotics induced cognitive and motor side effects with little separation from therapeutic-like doses. This study provides a uniform in vivo comparative basis on which to evaluate future early-stage drug candidates intended for potential pharmacotherapy of BPSD.

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Nano-hesperetin attenuates ketamine-induced schizophrenia-like symptoms in mice: participation of antioxidant parameters

et al. 2023

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Ketamine-enhanced immobility in forced swim test: A possible animal model for the negative symptoms of schizophrenia

Cited by 65 publications

References 76 publications

Doxycycline Ameliorates Schizophrenia-Like Behaviors in Experimental Models in Mice by Targeting Underlying Oxidative Stress

Doxycycline Ameliorates Schizophrenia-Like Behaviors in Experimental Models in Mice by Targeting Underlying Oxidative Stress

Antipsychotic, antidepressant, and cognitive-impairment properties of antipsychotics: rat profile and implications for behavioral and psychological symptoms of dementia

Nano-hesperetin attenuates ketamine-induced schizophrenia-like symptoms in mice: participation of antioxidant parameters

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