Impact of prepulse characteristics on the detection of sensorimotor gating deficits in schizophrenia

Braff, David L.; Geyer, Mark A.; Light, Gregory A.; Sprock, Joyce; Perry, William; Cadenhead, Kristin S.; Swerdlow, Neal R.

doi:10.1016/s0920-9964(00)00139-0

Cited by 267 publications

(179 citation statements)

References 33 publications

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“…The PPI paradigm employed in the present study is widely used for characterizing antipsychotic drugs, and has been claimed to possess face validity, since apomorphineinduced startle gating deficits in rats mimic the abnormalities of gating that are thought to underlie sensory flooding and cognitive fragmentation present in schizophrenic patients (McGhie and Chapman, 1961;Braff et al, 2001). These deficits can be reversed by 'typical' high-potency DA D 2 receptor antagonists and 'atypical' antipsychotics with low activity at 5-HT 1A receptors (Swerdlow et al, 1986(Swerdlow et al, , 1994Mansbach et al, 1988;Geyer et al, 2001).…”

Section: Discussionmentioning

confidence: 97%

Actions of Novel Antipsychotic Agents on Apomorphine-Induced PPI Disruption: Influence of Combined Serotonin 5-HT1A Receptor Activation and Dopamine D2 Receptor Blockade

Auclair

Kleven

Besnard

et al. 2006

Neuropsychopharmacol

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The dopamine D1/D2 agonist apomorphine (0.63 mg/kg) disrupted prepulse inhibition (PPI) of acoustic startle in rats, a model of sensorimotor gating deficits observed in schizophrenia. All current antipsychotics, which antagonize D 2 receptors, prevent this apomorphine-induced deficit. A novel class of antipsychotics possesses, in addition to D 2 antagonist property, various levels of 5-HT 1A agonist activity. Considering that the latter itself produces PPI deficits, it appeared necessary to assess the potential of this novel class of antipsychotics to reverse apomorphine-PPI deficits. Potent D 2 antagonists, like haloperidol (0.63-2.5 mg/kg), risperidone (0.63-10 mg/kg), and olanzapine (0.63-40 mg/kg) prevented apomorphine PPI disruption. The atypical antipsychotics, clozapine (40 mg/kg), nemonapride (0.01-2.5 mg/kg), ziprasidone (10 mg/kg), and aripiprazole (0.01 and 10 mg/kg), which all exhibit 5-HT 1A agonist properties, reversed PPI deficits at some doses only, whereas the anti-dyskinetic agent sarizotan (0.16-10 mg/kg), an efficacious 5-HT 1A agonist, did not. New generation antipsychotics with marked 5-HT 1A agonist properties, such as SLV313 and SSR181507 (0.0025-10 mg/kg and 0.16-10 mg/kg, respectively) did not reverse these deficits whereas bifeprunox (0.04-2.5 mg/kg) did. To reveal the contribution of 5-HT 1A agonist properties in the lack of effects of SLV313 and SSR181507, we pretreated rats with the 5-HT 1A antagonist WAY100635 (0.63 mg/kg). Under these conditions, significant reversal of PPI deficit was observed, indicating that D 2 antagonist properties of SLV313 and SSR181507 are now sufficient to overcome the disruptive effects of apomorphine. To summarize, antipsychotics possessing agonist efficacy at 5-HT 1A receptors exhibit diverse profiles against apomorphine-induced PPI deficits, depending on the balance between D 2 and 5-HT 1A activities, suggesting that they may display distinct activity on some aspects of gating deficits in schizophrenic patients.

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Section: Discussionmentioning

confidence: 97%

Actions of Novel Antipsychotic Agents on Apomorphine-Induced PPI Disruption: Influence of Combined Serotonin 5-HT1A Receptor Activation and Dopamine D2 Receptor Blockade

Auclair

Kleven

Besnard

et al. 2006

Neuropsychopharmacol

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“…PPI is a cross-species measure that refers to the ability of a non-startling ‘pre-stimulus’ to inhibit the response to a startling stimulus [366]. There have been numerous reports of PPI deficits in patients with schizophrenia [367,368]; however, exactly which endophenotype in schizophrenia is manifested as disrupted PPI remains debated [365]. Swerdlow and colleagues [368] persuasively suggested that PPI deficits are a useful psychophysiological outcome for basic studies in humans and animals to probe neural circuitry and as a pharmacological screen.…”

Section: Reviewmentioning

confidence: 99%

Reward circuitry dysfunction in psychiatric and neurodevelopmental disorders and genetic syndromes: animal models and clinical findings

Dichter

Damiano

Allen

2012

J Neurodevelop Disord

254

207

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This review summarizes evidence of dysregulated reward circuitry function in a range of neurodevelopmental and psychiatric disorders and genetic syndromes. First, the contribution of identifying a core mechanistic process across disparate disorders to disease classification is discussed, followed by a review of the neurobiology of reward circuitry. We next consider preclinical animal models and clinical evidence of reward-pathway dysfunction in a range of disorders, including psychiatric disorders (i.e., substance-use disorders, affective disorders, eating disorders, and obsessive compulsive disorders), neurodevelopmental disorders (i.e., schizophrenia, attention-deficit/hyperactivity disorder, autism spectrum disorders, Tourette’s syndrome, conduct disorder/oppositional defiant disorder), and genetic syndromes (i.e., Fragile X syndrome, Prader–Willi syndrome, Williams syndrome, Angelman syndrome, and Rett syndrome). We also provide brief overviews of effective psychopharmacologic agents that have an effect on the dopamine system in these disorders. This review concludes with methodological considerations for future research designed to more clearly probe reward-circuitry dysfunction, with the ultimate goal of improved intervention strategies.

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“…Since 1978 (30), PPI deficits have been consistently identified in schizophrenia patients (31). As is true for deficits of P50 suppression, PPI deficits extend beyond patients to their clinically unaffected relatives (32,33), and schizotypal (non-psychotic, unmedicated) patients (32,34).…”

Section: Neurophysiological Endophenotypesmentioning

confidence: 99%

“…PPI deficits correlate with distractibility (35), with quantitative measures of thought disorder (36) and with impaired function in schizophrenia patients (37). Much is known about the neural regulation of PPI by elements of cortico-striato-pallido-thalamic circuitry in humans and animal models (31,38,39). PPI may become a particularly valuable tool for screening novel therapeutic agents based on molecular targets identified by COGS (37,38,40).…”

Section: Neurophysiological Endophenotypesmentioning

confidence: 99%

Advances in endophenotyping schizophrenia

et al. 2008

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Impact of prepulse characteristics on the detection of sensorimotor gating deficits in schizophrenia

Cited by 267 publications

References 33 publications

Actions of Novel Antipsychotic Agents on Apomorphine-Induced PPI Disruption: Influence of Combined Serotonin 5-HT1A Receptor Activation and Dopamine D2 Receptor Blockade

Actions of Novel Antipsychotic Agents on Apomorphine-Induced PPI Disruption: Influence of Combined Serotonin 5-HT1A Receptor Activation and Dopamine D2 Receptor Blockade

Reward circuitry dysfunction in psychiatric and neurodevelopmental disorders and genetic syndromes: animal models and clinical findings

Advances in endophenotyping schizophrenia

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