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Titolo:
Pharmacological studies of prepulse inhibition models of sensorimotor gating deficits in schizophrenia: a decade in review
Autore:
Geyer, MA; Krebs-Thomson, K; Braff, DL; Swerdlow, NR;
Indirizzi:
Univ Calif San Diego, Dept Psychiat 0804, La Jolla, CA 92093 USA Univ Calif San Diego La Jolla CA USA 92093 t 0804, La Jolla, CA 92093 USA
Titolo Testata:
PSYCHOPHARMACOLOGY
fascicolo: 2-3, volume: 156, anno: 2001,
pagine: 117 - 154
Fonte:
ISI
Lingua:
ENG
Soggetto:
ACOUSTIC STARTLE REFLEX; PHENCYCLIDINE-INDUCED DISRUPTION; GLYCINE SITE ANTAGONIST; ATYPICAL ANTIPSYCHOTIC OLANZAPINE; 5-HT2A RECEPTOR ANTAGONIST; REARING-INDUCED DEFICITS; STRESSFUL LIFE EVENT; PRE-PULSE INHIBITION; D-AMPHETAMINE; ANIMAL-MODEL;
Keywords:
startle; prepulse inhibition; animal; rat; schizophrenia;
Tipo documento:
Review
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
214
Recensione:
Indirizzi per estratti:
Indirizzo: Geyer, MA Univ Calif San Diego, Dept Psychiat 0804, 9500 Gilman Dr, La Jolla, CA 92093 USA Univ Calif San Diego 9500 Gilman Dr La Jolla CA USA 92093 93 USA
Citazione:
M.A. Geyer et al., "Pharmacological studies of prepulse inhibition models of sensorimotor gating deficits in schizophrenia: a decade in review", PSYCHOPHAR, 156(2-3), 2001, pp. 117-154

Abstract

Rationale: Patients with schizophrenia exhibit deficits in an operational measure of sensorimotor gating: prepulse inhibition (PPI) of startle. Similar deficits in PPI are produced in rats by pharmacological or developmentalmanipulations. These experimentally induced PPI deficits in rats are clearly not animal models of schizophrenia per se, but appear to provide models of sensorimotor gating deficits in schizophrenia patients that have face, predictive, and construct validity. In rodents, disruptions in PPI of startle are produced by: stimulation of D-2 dopamine (DA) receptors, produced by amphetamine or apomorphine; activation of serotonergic systems, produced byserotonin (5-HT) releasers or direct agonists at multiple serotonin receptors; and blockade of N-methyl-D-aspartate (NMDA) receptors, produced by drugs such as phencyclidine (PCP). Accordingly, dopaminergic, serotonergic, and glutamatergic models of disrupted PPI have evolved and have been applied to the identification of potential antipsychotic treatments. In addition, some developmental manipulations, such as isolation rearing, have provided non-pharmacological animal models of the PPI deficits seen in schizophrenia. Objective: This review summarizes and evaluates studies assessing the effects of systemic drug administrations on PPI in rats. Methods: Studies examining systemic drug effects on PPI in rats prior to January 15, 2001 were compiled and organized into six annotated appendices. Based on this catalog of studies, the specific advantages and disadvantages of each of the four main PPI models used in the study of antipsychotic drugs were critically evaluated. Results: Despite some notable inconsistencies, the literature provides strong support for significant disruptions in PPI in rats produced by DAagonists, 5-HT, agonists, NMDA antagonists, and isolation rearing. Each ofthese models exhibits sensitivity to at least some antipsychotic medications. While the PPI model based on the effects of direct DA agonists is the most well-validated for the identification of known antipsychotics, the isolation rearing model also appears to be sensitive to both typical and atypical antipsychotics. The 5-HT PPI model is less generally sensitive to antipsychotic medications, but can provide insight into the contribution of serotonergic systems to the actions of newer antipsychotics that act upon multiple receptors. The deficits in PPI produced by NMDA antagonists appear to bemore sensitive to clozapine-like atypical antipsychotics than to typical antipsychotics. Hence, despite some exceptions to this generalization, the NMDA PPI model might aid in the identification of novel or atypical antipsychotic medications. Conclusions: Studies of drug effects on PPI in rats havegenerated four distinctive models that have utility in the identification of antipsychotic medications. Because each of these models has specific advantages and disadvantages, the choice of model to be used depends upon the question being addressed. This review should help to guide such decisions.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 17/01/20 alle ore 20:36:20