Effect of PDE10A inhibitors on MK-801-induced immobility in the forced swim test

Langen, Barbara; Dost, R.; Egerland, Ute; Stange, Hans; Hoefgen, Norbert

doi:10.1007/s00213-011-2567-y

Cited by 37 publications

(26 citation statements)

References 40 publications

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“…The enhancement of immobility after chronic administration of PCP (Noda et al, 1995), MK-801 (Langen et al, 2012), and ketamine (Chatterjee et al, 2011a) has been used previously as a model for the negative symptoms of psychosis, such as flattening of affect and avolition. Our observations indicated that chronic administration of BM reduced the immobility duration in the forced swim test, akin to clozapine.…”

Section: Discussionmentioning

confidence: 99%

Antipsychotic activity of standardizedBacopaextract against ketamine-induced experimental psychosis in mice: Evidence for the involvement of dopaminergic, serotonergic, and cholinergic systems

Chatterjee

Verma

Kumari

et al. 2015

Pharmaceutical Biology

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(2015) Antipsychotic activity of standardized Bacopa extract against ketamine-induced experimental psychosis in mice: Evidence for the involvement of dopaminergic, serotonergic, and cholinergic systems, Pharmaceutical Biology, 53:12, 1850-1860, DOI: 10.3109/13880209.2014 (40, 80, and 120 mg/kg, p.o.) were given to the mice 1 h prior to ketamine administration and tested for positive symptoms and cognitive deficits. A chronic ketamine treatment regimen was used to study the effect of BM on negative symptoms such as immobility enhancement. Each mouse was used once for the behavioral studies.Results: BM reduced ketamine-induced hyperactivity with an EC 50 value of 76.60 mg/kg. The 80 mg/kg dose was used for all other behavior analysis. Pretreatment with BM at 80 mg/kg showed two-fold increases in transfer latency time (TLT) in passive avoidance task. Chronic BM pretreatment (80 mg/kg p.o. daily Â 10 d) ameliorated the ketamine-induced enhanced immobility effect by 21% in the forced swim test. BM treatment reversed ketamine-induced increase in monoamine oxidase activity in both cortex and striatum and normalized the acetylcholinesterase activity and the glutamate levels in the hippocampus. Discussion and conclusion: Overall our findings suggest that BM possesses antipsychotic properties which might be due to its modulatory action on dopamine, serotonin, and glutamate neurotransmission.

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Section: Discussionmentioning

confidence: 99%

Antipsychotic activity of standardizedBacopaextract against ketamine-induced experimental psychosis in mice: Evidence for the involvement of dopaminergic, serotonergic, and cholinergic systems

Chatterjee

Verma

Kumari

et al. 2015

Pharmaceutical Biology

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“…[55]. Additionally, PDE10A inhibition led to reversal of MK-801-induced immobility in a forced swim test model, proposed to mimic negative symptoms in scz, using mice at 1 mg/kg po [56]. Interestingly, a recent report showed 6 induced significant akathisia-like behavior in nhp at 3 mg/ kg but not 1 mg/kg (Fig.…”

Section: Mp-10mentioning

confidence: 89%

The Use of PDE10A and PDE9 Inhibitors for Treating Schizophrenia

Tuttle

Kormos

2014

Small Molecule Therapeutics for Schizophrenia

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Schizophrenia (Scz) is a chronic and debilitating neurological disorder that afflicts approximately 1% of the general population with an increased incidence within families. Signs of this disorder typically appear between the ages of 16-30 although rare cases of childhood (<13) onset exist. Diagnosis of scz requires symptoms that persist for a duration of 1 month over a 6-month time period. The broad spectrum of symptoms are typically split into three categories: positive, negative, and cognitive. Implicit within these categories is the difficulty for stand-alone treatment methods, suggesting a combination of pharmacological and psychological treatment strategies is needed to manage this disease. Furthermore, while current pharmaceuticals are moderately effective at managing positive symptoms, the severe side effects lower patient compliance. Additionally, drugs used to treat negative and cognitive symptoms only have modest benefits, at best. Due to these limitations, there is a clear need for novel pharmaceuticals that modulate dysfunctional neurological pathways in scz patients. As such, both academic and pharmaceutical researchers are focused on identifying enzymes that can attenuate neurological signaling in disease-relevant brain regions. Specifically, this chapter will provide an in-depth review of current drug discovery efforts focused on inhibiting phosphodiesterase 10 and 9 (PDE10A, PDE9A, respectively).

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“…However, studies showing a deleterious effect of the repeated forced swim on cognitive tasks, such as the Morris water maze (Abel and Hannigan 1992, Rates 1998), novel object recognition (Yuen et al 2012), object location (Borsoi et al 2015a) and prepulse inhibition tests (Borsoi et al 2015a, b), contradict this successful strategy theory. On the other hand, immobility behavior in the forced swimming has been also related to schizophrenia negative symptoms, as apathy and lack of initiative (Langen et al 2012, Noda et al 1995, Porsolt et al 2010). …”

Section: Introductionmentioning

confidence: 99%

“…Similar results were described after repeated administration of another NMDAR antagonist, MK-801 (0.2 mg/kg/day for 15 days i.p. ): an increase on the immobility time which was blocked by antipsychotics administration (Kawaura et al 2015, 2016, Langen et al 2012, Rundfeldt et al 2000. These data lead to the use of the increase in the immobility time in the forced swimming as a tool to evaluate affective flattening in schizophrenia animal models (Neill et al 2014) and even for the development of new drug candidates (Porsolt et al 2010).…”

Section: Introductionmentioning

confidence: 99%

Is Forced Swimming Immobility a Good Endpoint for Modeling Negative Symptoms of Schizophrenia? - Study of Sub-Anesthetic Ketamine Repeated Administration Effects

Neves

Borsoi

Antonio

et al. 2017

An. Acad. Bras. Ciênc.

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Immobility time in the forced swimming has been described as analogous to emotional blunting or apathy and has been used for characterizing schizophrenia animal models. Several clinical studies support the use of NMDA receptor antagonists to model schizophrenia in rodents. Some works describe the effects of ketamine on immobility behavior but there is variability in the experimental design used leading to controversial results. In this study, we evaluated the effects of repeated administration of ketamine subanesthetic doses in forced swimming, locomotion in response to novelty and novel object recognition, aiming a broader evaluation of the usefulness of this experimental approach for modeling schizophrenia in mice. Ketamine (30 mg/kg/day i.p. for 14 days) induced a not persistent decrease in immobility time, detected 24h but not 72h after treatment. This same administration protocol induced a deficit in novel object recognition. No change was observed in mice locomotion. Our results confirm that repeated administration of sub-anesthetic doses of ketamine is useful in modeling schizophrenia-related behavioral changes in mice. However, the immobility time during forced swimming does not seem to be a good endpoint to evaluate the modeling of negative symptoms in NMDAR antagonist animal models of schizophrenia.

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Effect of PDE10A inhibitors on MK-801-induced immobility in the forced swim test

Cited by 37 publications

References 40 publications

Antipsychotic activity of standardizedBacopaextract against ketamine-induced experimental psychosis in mice: Evidence for the involvement of dopaminergic, serotonergic, and cholinergic systems

Antipsychotic activity of standardizedBacopaextract against ketamine-induced experimental psychosis in mice: Evidence for the involvement of dopaminergic, serotonergic, and cholinergic systems

The Use of PDE10A and PDE9 Inhibitors for Treating Schizophrenia

Is Forced Swimming Immobility a Good Endpoint for Modeling Negative Symptoms of Schizophrenia? - Study of Sub-Anesthetic Ketamine Repeated Administration Effects

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