Olfactory deficit as a result of clozapine withdrawal syndrome in an animal model of schizophrenia: preliminary results

Clozapine is an antipsychotic that produces serious withdrawal effects in schizophrenic patients. Olfactory deficits are well known as part of negative symptoms, but it is not known whether antipsychotic use and/or withdrawal are implicated. Then, we tested clozapine withdrawal in association with t...

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Published inAnais da Academia Brasileira de Ciências Vol. 90; no. 2; pp. 1659 - 1663
Main Authors Pacheco, Felipe D, Silva, Mauricio L DA, Batista, Graziela, Santos, Witória, Castro, Adalberto A DE, Canever, Lara, Zugno, Alexandra I
Format Journal Article
LanguageEnglish
Portuguese
Published Brazil Academia Brasileira de Ciências 01.04.2018
Subjects
animal model
Animals
Antipsychotic Agents - adverse effects
clozapine
Clozapine - adverse effects
Disease Models, Animal
Drug Therapy, Combination - methods
Ketamine - adverse effects
Male
MULTIDISCIPLINARY SCIENCES
Neuropsychological Tests
Olfaction Disorders - chemically induced
Olfaction Disorders - diagnosis
Olfactory deficit
Poly I-C - adverse effects
Preliminary Data
Rats, Wistar
schizophrenia
Schizophrenia - chemically induced
Substance Withdrawal Syndrome
clozapine
schizophrenia
animal model
Olfactory deficit
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Summary:Clozapine is an antipsychotic that produces serious withdrawal effects in schizophrenic patients. Olfactory deficits are well known as part of negative symptoms, but it is not known whether antipsychotic use and/or withdrawal are implicated. Then, we tested clozapine withdrawal in association with two widely used schizophrenia models: Neonatal immune challenge by Polycitidilic-polyinosinic acid (polyI:C) and ketamine. PolyI:C (or saline) was injected subcutaneously in neonatal period, dose of 5 mg/kg from 2 to 6 Post Natal Days, and ketamine or saline at the dose 25mg/kg intraperitoneally (i.p.), daily for 7 days from 53 to 60 post natal day. Clozapine 10mg/kg (or saline) was administered i.p. from 46 to 60 post natal day. Olfactory discrimination test (sensorial and cognitive deficit) was performed at 61 post natal day, 24h after the last injections. The association of PolyI:C, ketamine and clozapine disrupted Olfactory Discrimination, equating time in familiar and non-familiar compartments. PolyI:C plus ketamine increased crossings between compartments. It was produced, for the first time, an olfactory deficit induced by clozapine withdrawal in Wistar rats subjected to schizophrenia animal models.
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ISSN:0001-3765
1678-2690
1678-2690
DOI:10.1590/0001-3765201820170103