The effect of zotepine, risperidone, clozapine and olanzapine on MK-801-disrupted sensorimotor gating

Bubenikova, V.; Votava, Martin; Horáček, Jiří; Páleníček, Tomáš; Dockery, Colleen

doi:10.1016/j.pbb.2005.01.012

Cited by 80 publications

(60 citation statements)

References 29 publications

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“…However, modulation of dopaminergic activity is unlikely to be directly responsible for the disruptive effect of MK-801 on PPI, as MK-801 also disrupted PPI in wild-type and mutant D 1 and D 2 receptor knockout mice (Ralph-Williams et al, 2002), and typical antipsychotics with dopamine antagonist profiles do not restore MK-801-induced deficits in sensorimotor gating (Curzon and Decker, 1998;Martin et al, 2003). In the present study, the observation that the atypical antipsychotic clozapine restores MK-801-induced PPI disruption is in agreement with previous studies in rats and mice (Bakshi et al, 1994;Martin et al, 2003;Bubenikova et al, 2005) and provides a positive control for reversal of MK-801-induced sensorimotor gating deficits.…”

Section: Discussionsupporting

confidence: 92%

Cannabidiol Reverses MK-801-Induced Disruption of Prepulse Inhibition in Mice

Long

Malone

Taylor

2005

Neuropsychopharmacol

154

102

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Cannabidiol, a nonpsychoactive constituent of the Cannabis sativa plant, has been reported to act as an agonist of the vanilloid 1 channel in the transient receptor potential family (TRPV1) and also to inhibit the hydrolysis and cellular uptake of the endogenous cannabinoid anandamide. Cannabidiol has also been reported to have potential as an antipsychotic. We investigated the effect of cannabidiol on sensorimotor gating deficits in mice induced by the noncompetitive NMDA receptor antagonist, MK-801. Sensorimotor gating is deficient in psychotic disorders such as schizophrenia and may be reliably measured by prepulse inhibition (PPI) of the startle response in rodents and humans. MK-801 (0.3-1 mg/kg i.p.) dose dependently disrupted PPI while cannabidiol (1-15 mg/kg i.p.), when administered with vehicle, had no effect on PPI. Cannabidiol (5 mg/kg i.p.) successfully reversed disruptions in PPI induced by MK-801 (1 mg/kg i.p.), as did the atypical antipsychotic clozapine (4 mg/kg i.p.). Pretreatment with capsazepine (20 mg/kg i.p.) prevented the reversal of MK-801-induced disruption of PPI by cannabidiol, providing preliminary evidence that TRPV1 receptors are involved in the reversal of MK-801-induced sensorimotor gating deficits by cannabidiol.

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Section: Discussionsupporting

confidence: 92%

Cannabidiol Reverses MK-801-Induced Disruption of Prepulse Inhibition in Mice

Long

Malone

Taylor

2005

Neuropsychopharmacol

154

102

View full text Add to dashboard Cite

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“…In contrast, olanzapine (but not risperidone or haloperidol) is highly effective at reversing NMDA antagonist-induced PPI deficits, mostly in rodent models (Bakshi & Geyer, 1995;Duncan et al, 2000;Geyer et al, 2001). In general, rodent model studies show that NMDA antagonist-induced PPI deficits are selectively reversed by second-vs. first-generation antipsychotic medications (Bubenikova et al, 2005;Geyer & Ellenbroek, 2003;Geyer et al, 2001). The results from the current study are consistent with this animal literature in NMDA models.…”

Section: Discussionsupporting

confidence: 91%

Effects of olanzapine, risperidone and haloperidol on prepulse inhibition in schizophrenia patients: A double-blind, randomized controlled trial

Wynn

Green

Sprock

et al. 2007

Schizophrenia Research

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Prepulse inhibition (PPI), whereby the startle eyeblink response is inhibited by a relatively weak nonstartling stimulus preceding the powerful startle eliciting stimulus, is a measure of sensorimotor gating and has been shown to be deficient in schizophrenia patients. There is considerable interest in whether conventional and/or atypical antipsychotic medications can "normalize" PPI deficits in schizophrenia patients. 51 schizophrenia patients participated in a randomized, double-blind controlled trial on the effects of three commonly-prescribed antipsychotic medications (risperidone, olanzapine, or haloperidol) on PPI, startle habituation, and startle reactivity. Patients were tested at baseline, Week 4 and Week 8. Mixed model regression analyses revealed that olanzapine significantly improved PPI from Week 4 to Week 8, and that at Week 8 patients receiving olanzapine produced significantly greater PPI than those receiving risperidone, but not haloperidol. There were Contributors JKW, MFG, JS, GL, CW, CR, SE, SRM and DLB assisted with data collection. JS and GL provided quality assurance of the EMG data. JM assisted with data analysis. JKW, MFG and DLB drafted the manuscript and all authors provided comments and feedback on the manuscript.Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. no effects of medication on startle habituation or startle reactivity. These results support the conclusion that olanzapine effectively increased PPI in schizophrenia patients, but that risperidone and haloperidol had no such effects. The results are discussed in terms of animal models, neural substrates, and treatment implications. NIH Public Access

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“…However, given that the great majority of people with schizophrenia use tobacco, the necessity of nicotine as a co-treatment for this clinical effect remains unclear. In rats, it has been shown that clozapine by itself is effective in attenuating unimodal auditory PPI impairments due to NMDA glutamate blockade (Andreasen et al 2006;Ballmaier et al 2001;Bubenikova et al 2005;Geyer et al 2001;Linn et al 2003;Lipina et al 2005;Swerdlow et al 1996), although there are some contrary results that clozapine by itself does not significantly attenuate unimodal auditory PPI impairments caused by dizocilpine (Bast et al 2000;Hoffman et al 1993;Levin et al 2005). Bast et al showed that dizocilpine (0.1 mg/kg) impaired unimodal acoustic PPI and that this effect was not reversed by clozapine at a dose of 5 mg/kg (Bast et al 2000).…”

Section: Discussionmentioning

confidence: 99%

“…These have been related to abnormalities in sensory gating in general. A variety of studies with experimental animals show that clozapine reverses PPI-disruptive effects of NMDA antagonists in models of schizophrenia (Andreasen et al 2006;Ballmaier et al 2001;Bubenikova et al 2005;Linn et al 2003;Lipina et al 2005;Swerdlow et al 1996), However, there is little research determining the generality or specificity of sensory gating across modalities. Differential pharmacological effects in unimodal auditory PPI vs. crossmodal auditory-tactile PPI would indicate the involvement of differential neural systems in bases of these different measures of sensorimotor plasticity.…”

Section: Introductionmentioning

confidence: 99%

Clozapine treatment reverses dizocilpine-induced deficits of pre-pulse inhibition of tactile startle response

Levin

Caldwell

Perraut

2007

Pharmacology Biochemistry and Behavior

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Pre-pulse inhibition (PPI) is a phenomenon of neurobehavioral plasticity in which the motor response to a startling sensory stimulus is inhibited by a preceding sensory stimulus of a lower intensity. The current experiment used tactile startle rather than acoustic startle to determine the generality of PPI across sensory modalities. PPI is easily modeled in experimental animals and serves as a useful method for determining the neural bases for sensorimotor plasticity, which can be disturbed in sensory modulation disorders. In the current study, female Sprague-Dawley rats were tested for tactile startle PPI after an auditory pre-pulse. The glutamate NMDA receptor antagonist dizocilpine (MK-801, 0.05 mg/kg) caused a nearly total blockade of the PPI effect (p<0.0005). The antipsychotic drug clozapine (1.25 mg/kg, p<0.001 and 2.5 mg/kg p<0.05) significantly attenuated the dizocilpineinduced PPI impairment. Interestingly, the lower clozapine dose did not by self enhance PPI and the higher clozapine dose when given alone caused a significant (p<0.05) PPI impairment relative to control. Nicotine (0.2 and 0.4 mg/kg) did not significantly interact with the other treatments, though the higher nicotine dose did show a trend toward attenuating the PPI impairment caused by the high clozapine dose. These effects were replicated in a second experiment of clozapine-dizocilpine interactions without nicotine treatment. This study shows that PPI of tactile startle is dramatically impaired by blocking NMDA activation and that the prototypic atypical antipsychotic drug clozapine can correct this deficit. This may be relevant to the action of clozapine in attenuating sensory gating deficits in schizophrenia and may point to new avenues of treatment for sensory modulation disorders in which there is excessive tactile response.

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The effect of zotepine, risperidone, clozapine and olanzapine on MK-801-disrupted sensorimotor gating

Cited by 80 publications

References 29 publications

Cannabidiol Reverses MK-801-Induced Disruption of Prepulse Inhibition in Mice

Cannabidiol Reverses MK-801-Induced Disruption of Prepulse Inhibition in Mice

Effects of olanzapine, risperidone and haloperidol on prepulse inhibition in schizophrenia patients: A double-blind, randomized controlled trial

Clozapine treatment reverses dizocilpine-induced deficits of pre-pulse inhibition of tactile startle response

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