title: Neuroleptic drugs revert the contextual fear conditioning deficit presented by spontaneously hypertensive rats: a potential animal model of emotional context processing in schizophrenia?
abstract: Schizophrenia, bipolar disorder, and attention deficit/hyperactivity disorder (ADHD) present abnormalities in emotion processing. A previous study showed that the spontaneously hypertensive rats (SHR), a putative animal model of ADHD, present reduced contextual fear conditioning (CFC). The aim of the present study was to characterize the deficit in CFC presented by SHR. Adult male normotensive Wistar rats and SHR were submitted to the CFC task. Sensitivity of the animals to the shock and the CFC performance after repeated exposure to the task were investigated. Pharmacological characterization consisted in the evaluation of the effects of the following drugs administered previously to the acquisition of the CFC: pentylenetetrazole (anxiogenic) and chlordiazepoxide (anxiolytic); methylphenidate and amphetamine (used for ADHD); lamotrigine, carbamazepine, and valproic acid (mood stabilizers); haloperidol, ziprasidone, risperidone, amisulpride, and clozapine (neuroleptic drugs); metoclopramide and SCH 23390 (dopamine antagonists without antipsychotic properties); and ketamine (a psychotomimmetic). The effects of paradoxical sleep deprivation (that worsens psychotic symptoms) and the performance in a latent inhibition protocol (an animal model of schizophrenia) were also verified. No differences in the sensitivity to the shock were observed. The repeated exposure to the CFC task did not modify the deficit in CFC presented by SHR. Considering pharmacological treatments, only the neuroleptic drugs reversed this deficit. This deficit was potentiated by proschizophrenia manipulations. Finally, a deficit in latent inhibition was also presented by SHR. These findings suggest that the deficit in CFC presented by SHR could be a useful animal model to study abnormalities in emotional context processing related to schizophrenia.
authors.affiliation: Department of Pharmacology, Universidade Federal de São Paulo, Rua Botucatu, 862 Ed. Leal Prado, CEP 04023-062, São Paulo, Brazil.
authors.forename: Mariana Bendlin
authors.initials: MB
authors.lastname: Calzavara
authors.forename: Wladimir Agostini
authors.initials: WA
authors.lastname: Medrano
authors.forename: Raquel
authors.initials: R
authors.lastname: Levin
authors.forename: Sonia Regina
authors.initials: SR
authors.lastname: Kameda
authors.forename: Monica Levy
authors.initials: ML
authors.lastname: Andersen
authors.forename: Sergio
authors.initials: S
authors.lastname: Tufik
authors.forename: Regina Helena
authors.initials: RH
authors.lastname: Silva
authors.forename: Roberto
authors.initials: R
authors.lastname: Frussa-Filho
authors.forename: Vanessa Costhek
authors.initials: VC
authors.lastname: Abílio
mesh_terms: D000661:Amphetamine / Q000494:pharmacology; D000818:Animals; D014150:Antipsychotic Agents / Q000494:pharmacology*; D001522:Behavior, Animal / Q000187:drug effects; D003213:Conditioning, Psychological / Q000187:drug effects / Q000502:physiology; D004195:Disease Models, Animal; D018492:Dopamine Antagonists / Q000494:pharmacology; D004597:Electroshock; D004644:Emotions / Q000187:drug effects; D005239:Fear / Q000187:drug effects / Q000502:physiology; D046352:Freezing Reaction, Cataleptic / Q000187:drug effects; D007266:Inhibition, Psychological; D008297:Male; D008568:Memory / Q000187:drug effects; D017288:Pain Threshold / Q000187:drug effects; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D017208:Rats, Wistar; D012559:Schizophrenia / Q000175:diagnosis* / Q000188:drug therapy; D012565:Schizophrenic Psychology; D012892:Sleep Deprivation; D014828:Vocalization, Animal / Q000187:drug effects
chemical_list: D014150:Antipsychotic Agents; D018492:Dopamine Antagonists; D000661:Amphetamine