(+)-MK-801 induced social withdrawal in rats; a model for negative symptoms of schizophrenia

Rung, Johan P.; Carlsson, Arvid; Markinhuhta, Katarina Rydén; Carlsson, Maria

doi:10.1016/j.pnpbp.2005.03.004

Cited by 176 publications

(124 citation statements)

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“…The effects of ketamine induced disruptions (30 mg/kg ip ketamine daily for five consecutive days in Sprague-Dawley rats) also have been shown to be reversed by both clozapine and risperidone but not haloperidol and those of MK-801 (0.2 mg/kg given acutely 30 minute prior to testing) in male Sprague-Dawley rats have reportedly been reversed by dopamine stabilizers but not by clozapine or haloperidol (Rung et al, 2005). The dopamine stabilizer, OSU6162 has also demonstrated some improvements in reducing both positive and negative symptoms in schizophrenia patients (Gefvert et al, 2000).…”

Section: Effects Of Antipsychotic Drugs On the Social Interaction Testmentioning

confidence: 99%

“…MK-801 has been shown in some but not all studies to produce similar deficits in social behaviours in adult male rats following both acute treatment (0.2 mg/kg, ip; Rung et al, 2005) and a sub-chronic dosing regime (0.13 mg/kg/day ip for 14 days; Matsuoka et al, 2005). Sams-Dodd in 2004 used different dosing regimes of MK-801 (group 1: 0.063 or 0.5 mg/kg for 7 days, s.c with mini osmotic pumps) where the rats were tested in the social interaction test 21 days post drug administration and (group 2: 5mg/kg of MK-801, on alternate days for 4 days) with the rats were being tested following a 7 day washout period.…”

mentioning

confidence: 98%

“…The concept of translatability is closely associated with face validity or resemblance between behaviours observed by the subject in an animal model and those of the human condition. Face validity in the context of the social interaction test with NMDA antagonist is deemed fairly accurate with most manipulations successfully interfering with normal social interaction in animals using either PCP (Sams-Dodd et al, 2005, Snigdha et al, 2008a ketamine or MK01 (Rung et al, 2005) and resulting in deficits similar to that seen in patients with schizophrenia (Andreason et al, 1990). An extensive literature search reveals that of all the NMDA antagonists that are used to induce social interaction deficits, phencyclidine (PCP) is the most commonly used, followed by MK-801 and ketamine.…”

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confidence: 99%

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Animal models of cognitive dysfunction and negative symptoms of schizophrenia: Focus on NMDA receptor antagonism

Neill

Barnes

Cook

et al. 2010

Pharmacology & Therapeutics

473

322

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Cognitive deficits in schizophrenia remain an unmet clinical need. Improved understanding of the neuro-and psychopathology of these deficits depends on the availability of carefully validated animal models which will assist the development of novel therapies. There is much evidence that at least some of the pathology and symptomatology (particularly cognitive and negative symptoms) of schizophrenia results from a dysfunction of the glutamatergic system which may be modelled in animals through the use of NMDA receptor antagonists. The current review examines the validity of this model in rodents. We review the ability of acute and sub-chronic treatment with three non-competitive NMDA antagonists; phencyclidine (PCP), ketamine and MK801 (dizocilpine) to produce cognitive disturbances of relevance to schizophrenia in rodents and their subsequent reversal by first-and second-generation antipsychotic drugs. Effects of NMDA receptor antagonists on the performance of rodents in behavioural tests assessing the various domains of cognition and negative symptoms are examined: novel object recognition for visual memory, reversal learning and attentional set shifting for problem solving and reasoning, 5-choice serial reaction time for attention and speed of processing; in addition to effects on social behaviour and neuropathology. The evidence strongly supports the use of NMDA receptor antagonists to model cognitive deficit and negative symptoms of schizophrenia as well as certain pathological disturbances seen in the illness. This will facilitate the evaluation of much-needed novel therapies for improved therapy of cognitive deficits and negative symptoms in schizophrenia.

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Section: Effects Of Antipsychotic Drugs On the Social Interaction Testmentioning

confidence: 99%

mentioning

confidence: 98%

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confidence: 99%

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Animal models of cognitive dysfunction and negative symptoms of schizophrenia: Focus on NMDA receptor antagonism

Neill

Barnes

Cook

et al. 2010

Pharmacology & Therapeutics

473

322

View full text Add to dashboard Cite

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“…MK-801 is a non-competitive NMDA receptor antagonist that is used as a model for schizophrenia because it mimics both positive and negative symptoms of the disorder [58]. MK-801 is a potent cognition impairer, but sensory, locomotor and toxicological side effects have been shown to become problematic with doses higher than 1 mg/kg and may already influence ORT performance at lower doses [40,59].…”

Section: Pharmacological Deficit Modelsmentioning

confidence: 99%

Object recognition testing: Methodological considerations on exploration and discrimination measures

Akkerman

Blokland

Reneerkens

et al. 2012

Behavioural Brain Research

175

123

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“…MK801 acts within the NMDA calcium channel in a manner similar to phencyclidine (PCP) and ketamine, and can produce psychosis [37], catalepsy, analgesia, and locomotor hyperactivity. Indeed, most noncompetitive NMDAR antagonists, because of their similarity to PCP, have been proposed as animal models of schizophrenia [38]. As with PCP, MK801 induces large neuronal vacuoles (Olney's lesions) within 30 min of administration [39].…”

Section: Introductionmentioning

confidence: 99%

The competitive NMDA receptor antagonist CPP disrupts cocaine-induced conditioned place preference, but spares behavioral sensitization

Carmack

Kim²,

Sage³

et al. 2013

Behavioural Brain Research

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h i g h l i g h t sCPP co-administration with cocaine altered the acute response to cocaine. NMDAR antagonism with CPP had no effect on cocaine-induced behavioral sensitization. NMDAR antagonism with CPP abolished cocaine-induced conditioned place preference. a r t i c l e i n f o a b s t r a c tRecently, the notion that memory and addiction share similar neural substrates has become widely accepted. N-methyl-d-aspartate receptors (NMDAR) are the cornerstones of synaptic models of memory. The present study examined the effect of the competitive NMDAR antagonist CPP on the induction of behavioral sensitization and conditioned place preference to cocaine. Conditioned place preference is an associative memory model of drug seeking, while sensitization is a non-associative model of the transition from casual to compulsive use. There were three principal findings: (1) co-administration of CPP and cocaine altered the acute response to cocaine, suggesting a direct interaction between the two drugs; (2) NMDAR antagonism had no effect on behavioral sensitization; and (3) NMDAR antagonism abolished conditioned place preference. A review of prior evidence supporting a role for NMDARs in sensitization suggests that NMDAR antagonists directly interfere with cocaine's psychostimulant effects, and this interaction could be misinterpreted as a disruption of sensitization. Finally, we suggest that addiction recruits multiple kinds of plasticity, with sensitization recruiting NMDAR-independent mechanisms.

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(+)-MK-801 induced social withdrawal in rats; a model for negative symptoms of schizophrenia

Cited by 176 publications

References 32 publications

Animal models of cognitive dysfunction and negative symptoms of schizophrenia: Focus on NMDA receptor antagonism

Animal models of cognitive dysfunction and negative symptoms of schizophrenia: Focus on NMDA receptor antagonism

Object recognition testing: Methodological considerations on exploration and discrimination measures

The competitive NMDA receptor antagonist CPP disrupts cocaine-induced conditioned place preference, but spares behavioral sensitization

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