The monotonic dependency of prepulse inhibition of the acoustic startle reflex on the intensity of the startle-eliciting stimulus

Csomor, Philipp A.; Yee, Benjamin K.; Quednow, Boris B.; Stadler, Renée R.; Feldon, Joram; Vollenweider, Franz X.

doi:10.1016/j.bbr.2006.07.016

Cited by 19 publications

(23 citation statements)

References 33 publications

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“…Bortolato et al 2007;Crawley et al 1997;McCaughran et al 1997;Paylor and Crawley 1997). This is of significant concern because differences in the baseline startle reactivity can seriously complicate or confound the interpretation of the results obtained on PPI (Csomor et al 2006(Csomor et al , 2008Hoffman and Searle 1965;Swerdlow et al 2000;Yee et al 2005). The dependency of PPI magnitude on baseline startle reactivity has been demonstrated in rodents and humans (Csomor et al 2006(Csomor et al , 2008Hince and MartinIverson 2005;Yee et al 2005)-a finding that has been incorporated also by computational models of PPI (Sandner and Canal 2007;Schmajuk and Larrauri 2005).…”

Section: Introductionmentioning

confidence: 87%

“…The dependency of PPI magnitude on baseline startle reactivity has been demonstrated in rodents and humans (Csomor et al 2006(Csomor et al , 2008Hince and MartinIverson 2005;Yee et al 2005)-a finding that has been incorporated also by computational models of PPI (Sandner and Canal 2007;Schmajuk and Larrauri 2005). The present study was undertaken to initially address the confounding phenotype on startle reactivity in comparison with C57BL/6 mice using a more stringent parametric design of PPI assessment incorporating multiple pulse intensities (Csomor et al 2006(Csomor et al , 2008Yee et al 2005). With this PPI design, we went on to investigate if the DBA/2 substrain may enjoy superior sensitivity (compared with C57BL/6 mice) in the detection of atypical neuroleptic drugs using clozapine as the reference compound.…”

Section: Introductionmentioning

confidence: 97%

“…This is of significant concern because differences in the baseline startle reactivity can seriously complicate or confound the interpretation of the results obtained on PPI (Csomor et al 2006(Csomor et al , 2008Hoffman and Searle 1965;Swerdlow et al 2000;Yee et al 2005). The dependency of PPI magnitude on baseline startle reactivity has been demonstrated in rodents and humans (Csomor et al 2006(Csomor et al , 2008Hince and MartinIverson 2005;Yee et al 2005)-a finding that has been incorporated also by computational models of PPI (Sandner and Canal 2007;Schmajuk and Larrauri 2005). The present study was undertaken to initially address the confounding phenotype on startle reactivity in comparison with C57BL/6 mice using a more stringent parametric design of PPI assessment incorporating multiple pulse intensities (Csomor et al 2006(Csomor et al , 2008Yee et al 2005).…”

Section: Introductionmentioning

confidence: 99%

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Are DBA/2 mice associated with schizophrenia-like endophenotypes? A behavioural contrast with C57BL/6 mice

2009

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Relative to the C57BL/6 strain, DBA/2 mice displayed multiple behavioural traits relevant to schizophrenia psycho- and physiopathology, indicative of both dopaminergic and glutamatergic/N-methyl-D: -aspartic acid receptor dysfunctions. Further examination of their underlying neurobiological differences is therefore warranted in order to enhance the power of this specific inter-strain comparison as a model of schizophrenia.

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Section: Introductionmentioning

confidence: 87%

Section: Introductionmentioning

confidence: 97%

Section: Introductionmentioning

confidence: 99%

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Are DBA/2 mice associated with schizophrenia-like endophenotypes? A behavioural contrast with C57BL/6 mice

2009

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“…Given the known differences between mice and rats in the modulation of PPI by different subtypes of dopamine receptors (e.g., Doherty et al 2008; Ralph-Williams et al 2003), it is of fundamental importance to ascertain whether the robust PPI-disruptive effect of scopolamine seen in rats is translatable to mice. Moreover, three of the five mice studies quoted in Table 1 reported a confounding increase in startle reactivity that could complicate interpretation of PPI data because there is ample evidence for a dependency of PPI on the baseline startle reactivity in mice as well as humans (Csomor et al 2006, 2008; Yee et al 2005). …”

Section: Introductionmentioning

confidence: 99%

Reversal of scopolamine-induced disruption of prepulse inhibition by clozapine in mice

Singer

Yee

2012

Pharmacology Biochemistry and Behavior

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Prepulse inhibition (PPI) of the acoustic startle reflex refers to the reduction of the startle response to an intense acoustic pulse stimulus when it is shortly preceded by a weak non-startling prepulse stimulus and provides a cross-species measure of sensory-motor gating. PPI is typically impaired in schizophrenia patients, and a similar impairment can be induced in rats by systemic scopolamine, a muscarinic cholinergic receptor antagonist that can evoke a range of cognitive and psychotic symptoms in healthy humans that are commonly referred to as the “anti-muscarinic syndrome” resembling some clinical features of schizophrenia. Scopolamine-induced PPI disruption has therefore been proposed as an anti-muscarinic animal model of schizophrenia, but parallel investigations in the mouse remain scant and the outcomes are mixed and often confounded by an elevation of startle reactivity. Here, we distinguished the PPI-disruptive and the confounding startle-enhancing effects of scopolamine (1 and 10 mg/kg, i.p.) in C57BL/6 wild-type mice by showing that the latter partly stemmed from a shift in spontaneous baseline reactivity. With appropriate correction for between-group differences in startle reactivity, we went on to confirm that the PPI-disruptive effect of scopolamine could be nullified by clozapine pre-treatment (1.5 mg/kg, i.p.) in a dose-dependent manner. This is the first demonstration that scopolamine-induced PPI disruption is sensitive to atypical antipsychotic drugs. In concert with previous data showing its sensitivity to haloperidol the present finding supports the predictive validity of the anti-muscarinic PPI disruption model for both typical and atypical antipsychotic drug action.

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“…The reduction of startle magnitude on prepulse+pulse condition compared with pulse-alone condition is divided by the latter and expressed in percent, i.e., %PPI = (prepulse+pulse startle – pulse-alone) × 100%. This proportion measure is sensitive to independent changes in startle reactivity obtained on pulse-alone condition in humans (Csomor et al 2006) as well as rodents (Yee et al 2005). Interpretation of this measure would not be straightforward in the presence of a notable treatment effect on baseline startle reaction.…”

Section: Behavioural Evaluationmentioning

confidence: 99%

A conceptual and practical guide to the behavioural evaluation of animal models of the symptomatology and therapy of schizophrenia

Yee

Singer

2013

Cell Tissue Res

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Schizophrenia is a chronic debilitating brain disorder characterized by a complex set of perceptual and behavioural symptoms that severely disrupt and undermine the patient’s psychological well-being and quality of life. Since the exact disease mechanisms remain essentially unknown, holistic animal models are indispensable tools for any serious investigation into the neurobiology of schizophrenia, including the search of remedies, prevention, and possible biological markers. This review provides some practical advice to those confronted with the task of evaluating their animal models for relevance to schizophrenia that inevitably involves behavioural tests with animals. To a novice, this challenge is not only a technical one, as it also entails attention to interpretative issues concerning validity and translational power. Here, we attempt to offer some guidance to help overcome these obstacles by drawing on our experience on diverse animal models of schizophrenia based on genetics, strain difference, brain lesions, pharmacological induction, and early life developmental manipulations. The review pays equal emphasis on the general (theoretical) considerations in experimental design and the illustration of the problematics related to test parameters and data analysis of selected exemplar behavioural tests. Finally, the individual difference of behavioural expression in relevant tests observed in wild type animals may offer an alternative approach to explore the mechanism of schizophrenia-related behavioural dysfunction at the molecular, cellular and structural levels that are of more immediate relevance to cell and tissue research.

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The monotonic dependency of prepulse inhibition of the acoustic startle reflex on the intensity of the startle-eliciting stimulus

Cited by 19 publications

References 33 publications

Are DBA/2 mice associated with schizophrenia-like endophenotypes? A behavioural contrast with C57BL/6 mice

Are DBA/2 mice associated with schizophrenia-like endophenotypes? A behavioural contrast with C57BL/6 mice

Reversal of scopolamine-induced disruption of prepulse inhibition by clozapine in mice

A conceptual and practical guide to the behavioural evaluation of animal models of the symptomatology and therapy of schizophrenia

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