title: Spontaneously Hypertensive Rats (SHR) present deficits in prepulse inhibition of startle specifically reverted by clozapine.
abstract: Deficits in an operational measure of sensorimotor gating - the prepulse inhibition of startle (PPI) - are presented in psychiatric disorders such as schizophrenia, bipolar disorder, and attention deficit/hyperactivity disorder (ADHD). Some previous studies showed that the spontaneously hypertensive rats (SHR) present PPI deficit. Although SHR is suggested as an animal model to study ADHD, we have suggested that the behavioral phenotype of this strain mimics some aspects of schizophrenia. The aim of this study was to characterize the PPI response in SHR. Pharmacological characterization consisted in the evaluation of the effects of the following drugs administered to adult Wistar rats (WR) and SHR previously to the PPI test: amphetamine (used for ADHD and also a psychotomimetic drug), haloperidol and clozapine (antipsychotic drugs), metoclopramide (dopamine antagonist without antipsychotic properties) and carbamazepine (mood stabilizer). Our results showed that SHR presented reduced PPI. This deficit was similar to that induced by amphetamine in WR. Only the atypical antipsychotic clozapine improved the PPI deficit observed in SHR. These findings reinforce the SHR strain as an animal model to study several aspects of schizophrenia, including the abnormalities in sensorimotor gating associated with this disease.
authors.affiliation: Department of Pharmacology, Universidade Federal de São Paulo. Rua Pedro de Toledo, 669, 5 ° andar, Ed. de Pesquisas II, CEP 04039-032, São Paulo, SP, Brazil.
authors.forename: Raquel
authors.initials: R
authors.lastname: Levin
authors.forename: Mariana Bendlin
authors.initials: MB
authors.lastname: Calzavara
authors.forename: Camila Maurício
authors.initials: CM
authors.lastname: Santos
authors.forename: Wladimir Agostini
authors.initials: WA
authors.lastname: Medrano
authors.forename: Suzy Tamie
authors.initials: ST
authors.lastname: Niigaki
authors.forename: Vanessa Costhek
authors.initials: VC
authors.lastname: Abílio
mesh_terms: D000161:Acoustic Stimulation; D000661:Amphetamine / Q000494:pharmacology / Q000627:therapeutic use; D000818:Animals; D018692:Antimanic Agents / Q000494:pharmacology / Q000627:therapeutic use; D014150:Antipsychotic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D002220:Carbamazepine / Q000494:pharmacology / Q000627:therapeutic use; D003024:Clozapine / Q000494:pharmacology / Q000627:therapeutic use; D004195:Disease Models, Animal; D018492:Dopamine Antagonists / Q000494:pharmacology; D018765:Dopamine Uptake Inhibitors / Q000494:pharmacology; D008297:Male; D008787:Metoclopramide / Q000494:pharmacology / Q000627:therapeutic use; D051381:Rats; D011918:Rats, Inbred SHR; D017208:Rats, Wistar; D013216:Reflex, Startle / Q000187:drug effects / Q000502:physiology*; D012559:Schizophrenia / Q000188:drug therapy* / Q000503:physiopathology; D055139:Sensory Gating / Q000187:drug effects / Q000502:physiology*
chemical_list: D018692:Antimanic Agents; D014150:Antipsychotic Agents; D018492:Dopamine Antagonists; D018765:Dopamine Uptake Inhibitors; D002220:Carbamazepine; D000661:Amphetamine; D003024:Clozapine; D008787:Metoclopramide