Assessing the Validity of an Animal Model of Deficient Sensorimotor Gating in Schizophrenic Patients

Swerdlow, Neal R.

doi:10.1001/archpsyc.1994.03950020063007

Cited by 677 publications

(404 citation statements)

References 67 publications

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“…The original dopamine model focused primarily on testing the ability of antipsychotic drugs to block the PPI-disruptive effects of apomorphine in rats (Swerdlow et al, 1994). In sum, these effects of apomorphine in rats are reliably prevented by virtually all antipsychotics that have appreciable affinity for dopamine D 2 receptors.…”

Section: The Dopamine Prepulse Inhibition Model In Ratsmentioning

confidence: 99%

“…In sum, these effects of apomorphine in rats are reliably prevented by virtually all antipsychotics that have appreciable affinity for dopamine D 2 receptors. Swerdlow et al (1994) have shown an excellent correlation between the clinical potency of an antipsychotic and its ability to block the PPIdisruptive effects of the dopamine agonist apomorphine in rats. Although this finding provides important validation of the predictive validity of the dopamine PPI model for antipsychotic drugs, it primarily reflects the importance of dopamine D 2 antagonism in antipsychotic drug action and therefore only recapitulates in a behavioral paradigm what was already known from simple ligand-binding assays.…”

Section: The Dopamine Prepulse Inhibition Model In Ratsmentioning

confidence: 99%

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The family of sensorimotor gating disorders: Comorbidities or diagnostic overlaps?

2006

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Prepulse inhibition (PPI) of startle is an operational measure of the pre-attentive filtering process known as sensorimotor gating. Originally identified in patients with schizophrenia, PPI deficits have been observed in multiple but not all psychiatric disorders. Thus, as with most signs and symptoms of psychiatric disorders, deficits in PPI cut across diagnostic categories. It remains unclear whether the diversity of disorders exhibiting deficient PPI bespeaks diagnostic overlaps or comorbidities. Given the recent focus on treatments for cognitive deficits of schizophrenia independently of treating psychosis, the relationship of PPI deficits to cognitive deficits becomes of interest. Although PPI cannot be considered to be a cognitive process per se, abnormalities in pre-attentive information processing may be predictive of or lead to complex cognitive deficits. Animal models of PPI deficits produced by dopamine agonists reliably predict existing antipsychotics. Nevertheless, since neither PPI nor cognitive deficits in schizophrenia are ameliorated by standard antipsychotics, current research is exploring the predictive value of non-dopaminergic PPI models in identifying treatments for gating disturbances independently of their relevance to specific disorders. Both PPI and cognitive deficits in schizophrenia patients are not reversed by first generation antipsychotics but may be attenuated by clozapine. Similarly, effects of glutamate antagonists on symptoms in patients and PPI in animals appear to be reduced by clozapine. Hence, treatment-induced reversals of deficits in PPI produced by glutamate antagonists may provide animal, and human, models to aid in the discovery of treatments of cognitive deficits in patients already treated with existing antipsychotics.

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Section: The Dopamine Prepulse Inhibition Model In Ratsmentioning

confidence: 99%

Section: The Dopamine Prepulse Inhibition Model In Ratsmentioning

confidence: 99%

The family of sensorimotor gating disorders: Comorbidities or diagnostic overlaps?

2006

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“…PPI has been found to be abnormal in schizophrenia patients and in their relatives, and appears to be under significant genetic control (Braff and Geyer, 1990;Cadenhead et al, 2000;Anokhin et al, 2003;Kumari and Postma, 2005;Hong et al, 2007). PPI has increasingly been used as a surrogate index of psychosis in animal models (Swerdlow et al, 1994;Braff et al, 2001). However, PPI abnormality is not specific to schizophrenia or psychosis since it is also associated with several other psychiatric conditions including stress, bipolar disorder with psychotic features, panic disorder, obsessive-compulsive disorder, dementia, and autism (Grillon and Davis, 1997;Perry et al, 2001Perry et al, , 2007Ludewig et al, 2002;Hoenig et al, 2005;Ueki et al, 2006).…”

Section: Introductionmentioning

confidence: 99%

Nicotine Effect on Prepulse Inhibition and Prepulse Facilitation in Schizophrenia Patients

Hong

Wonodi

Lewis

et al. 2007

Neuropsychopharmacol

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Acoustic prepulse inhibition (PPI) is considered an important biomarker in animal studies of psychosis and a number of psychiatric conditions. Nicotine has been shown to improve acoustic PPI in some animal strains and in humans. However, there is little data on effects of nicotine on acoustic PPI in schizophrenia patients using a double-blind, placebo-controlled study design. The primary aim of the current study was to test the effect of nicotine nasal spray on acoustic PPI in schizophrenia patients. The secondary aim was to test nicotine effect on prepulse facilitation (PPF). The study included 18 schizophrenia patient smokers and 12 healthy control smokers, tested in a double-blind, placebo-controlled, crossover, randomized design immediately after nicotine or saline placebo nasal sprays. PPI was tested using 120 ms prepulse-pulse interval. PPF was tested using 4500 ms prepulse-pulse interval. The results showed a significant main effect of drug on PPI in that nicotine improved PPI compared to placebo (p ¼ 0.008) with no drug by diagnosis interaction (p ¼ 0.90). Improvement in PPI in response to nicotine was significantly correlated with the baseline severity of clinical symptoms (r ¼ 0.59, p ¼ 0.02) in patients. There was no significant drug or drug by diagnosis interaction for the 4500 ms prepulse-pulse interval condition. However, nicotine improved inhibition in a subgroup of subjects exhibiting PPF (p ¼ 0.002). In conclusion, the findings confirmed that nicotine transiently improves acoustic PPI in schizophrenia patients. Additionally, schizophrenia patients with more clinical symptoms may have benefited more from nicotinic effect on PPI.

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“…PPI of the ASR is an attenuation of the startle amplitude by a non-startling prepulse preceding the startle-eliciting pulse by a certain amount of time, and is considered an operational measure of sensorimotor gating (eg Graham, 1975;Geyer et al, 1990;Swerdlow et al, 1994). Habituation is a reduction over time of the amplitude of the ASR, seen after repeated presentation of identical startle eliciting pulses, which is not a result of sensory adaptation or muscle fatigue, and is considered a form of non-associative learning (Christoffersen, 1997).…”

Section: Introductionmentioning

confidence: 99%

The Effects of Increased Central Serotonergic Activity on Prepulse Inhibition and Habituation of the Human Startle Response

Jensen

Oranje

Wienberg

et al. 2007

Neuropsychopharmacol

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Sensorimotor gating is critical to normal brain functioning, and disruptions are associated with certain mental illnesses, such as schizophrenia. Prepulse inhibition of the acoustic startle reflex (ASR) (PPI) is an operational measure of sensorimotor gating, of which evidence for a serotonergic modulation is currently inconsistent. In a double-blind placebo-controlled crossover design, 18 healthy male volunteers received either placebo or a dose of 10 mg of escitalopram (SSRI), after which they were tested in both PPI and habituation of the startle reflex paradigms. No significant differences between the two treatments were observed on PPI, although escitalopram was found to significantly delay habituation of the ASR. In the current study, escitalopram was found to delay habituation, but it did not affect PPI in healthy male volunteers. As escitalopram is a highly specific SSRI, the results suggest that an increased serotonergic activity disrupts habituation, but not PPI in healthy volunteers.

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Assessing the Validity of an Animal Model of Deficient Sensorimotor Gating in Schizophrenic Patients

Cited by 677 publications

References 67 publications

The family of sensorimotor gating disorders: Comorbidities or diagnostic overlaps?

The family of sensorimotor gating disorders: Comorbidities or diagnostic overlaps?

Nicotine Effect on Prepulse Inhibition and Prepulse Facilitation in Schizophrenia Patients

The Effects of Increased Central Serotonergic Activity on Prepulse Inhibition and Habituation of the Human Startle Response

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