title: Electroencephalographic study of chlorpromazine alone or combined with alpha-lipoic acid in a model of schizophrenia induced by ketamine in rats.
abstract: Schizophrenia is characterized by behavioral symptoms, brain function impairments and electroencephalographic (EEG) changes. Dysregulation of immune responses and oxidative imbalance underpins this mental disorder. The present study aimed to investigate the effects of the typical antipsychotic chlorpromazine (CP) alone or combined with the natural antioxidant alpha-lipoic acid (ALA) on changes in the hippocampal average spectral power induced by ketamine (KET). Three days after stereotactic implantation of electrodes, male Wistar rats were divided into groups treated for 10 days with saline (control) or KET (10 mg/kg, IP). CP (1 or 5 mg/kg, IP) alone or combined with ALA (100 mg/kg, P.O.) was administered 30 min before KET or saline. Hippocampal EEG recordings were taken on the 1st, 5th and 10th days of treatment immediately after the last drug administration. KET significantly increased average spectral power of delta and gamma-high bands on the 5th and 10th days of treatment when compared to control. Gamma low-band significantly increased on the 1st, 5th and 10th days when compared to control group. This effect of KET was prevented by CP alone or combined with ALA. Indeed, the combination of ALA 100 + CP1 potentiated the inhibitory effects of CP1 on gamma low-band oscillations. In conclusion, our results showed that KET presents excitatory and time-dependent effects on hippocampal EEG bands activity. KET excitatory effects on EEG were prevented by CP alone and in some situations potentiated by its combination with ALA.
authors.affiliation: Drug Research and Development Center, Department of Physiology and Pharmacology, School of Medicine, Federal University of Ceará, Fortaleza, Ceará, Brazil; Health Science Center, School of Nursing, University of Fortaleza, Fortaleza, Ceará, Brazil.
authors.forename: Luis Rafael Leite
authors.initials: LRL
authors.lastname: Sampaio
authors.affiliation: Drug Research and Development Center, Department of Physiology and Pharmacology, School of Medicine, Federal University of Ceará, Fortaleza, Ceará, Brazil; Health Science Center, School of Nursing, University of Fortaleza, Fortaleza, Ceará, Brazil.
authors.forename: Lucas Teixeira Nunes
authors.initials: LTN
authors.lastname: Borges
authors.affiliation: Drug Research and Development Center, Department of Physiology and Pharmacology, School of Medicine, Federal University of Ceará, Fortaleza, Ceará, Brazil.
authors.forename: Talita Matias
authors.initials: TM
authors.lastname: Barbosa
authors.affiliation: Drug Research and Development Center, Department of Physiology and Pharmacology, School of Medicine, Federal University of Ceará, Fortaleza, Ceará, Brazil.
authors.forename: Natalia Castelo Branco
authors.initials: NCB
authors.lastname: Matos
authors.affiliation: Drug Research and Development Center, Department of Physiology and Pharmacology, School of Medicine, Federal University of Ceará, Fortaleza, Ceará, Brazil.
authors.forename: Ricardo de Freitas
authors.initials: RF
authors.lastname: Lima
authors.affiliation: Health Science Center, School of Nursing, University of Fortaleza, Fortaleza, Ceará, Brazil.
authors.forename: Mariana Nascimento de
authors.initials: MN
authors.lastname: Oliveira
authors.affiliation: Drug Research and Development Center, Department of Physiology and Pharmacology, School of Medicine, Federal University of Ceará, Fortaleza, Ceará, Brazil.
authors.forename: Viviane Nóbrega
authors.initials: VN
authors.lastname: Gularte
authors.affiliation: Health Science Center, School of Medicine, University Centre Christus, Fortaleza, Ceará, Brazil.
authors.forename: Manoel Cláudio Azevedo
authors.initials: MCA
authors.lastname: Patrocínio
authors.affiliation: Drug Research and Development Center, Department of Physiology and Pharmacology, School of Medicine, Federal University of Ceará, Fortaleza, Ceará, Brazil.
authors.forename: Danielle
authors.initials: D
authors.lastname: Macêdo
authors.affiliation: Drug Research and Development Center, Department of Physiology and Pharmacology, School of Medicine, Federal University of Ceará, Fortaleza, Ceará, Brazil.
authors.forename: Otoni Cardoso do
authors.initials: OCD
authors.lastname: Vale
authors.affiliation: Drug Research and Development Center, Department of Physiology and Pharmacology, School of Medicine, Federal University of Ceará, Fortaleza, Ceará, Brazil. Electronic address: silvania_vasconcelos@yahoo.com.br.
authors.forename: Silvânia Maria Mendes de
authors.initials: SMM
authors.lastname: Vasconcelos
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D014150:Antipsychotic Agents / Q000494:pharmacology*; D001921:Brain / Q000187:drug effects* / Q000503:physiopathology; D002746:Chlorpromazine / Q000494:pharmacology*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004353:Drug Evaluation, Preclinical; D004359:Drug Therapy, Combination; D000069280:Electrocorticography; D004567:Electrodes, Implanted; D007649:Ketamine; D008297:Male; D011897:Random Allocation; D017208:Rats, Wistar; D012559:Schizophrenia / Q000188:drug therapy* / Q000503:physiopathology; D008063:Thioctic Acid / Q000494:pharmacology*; D013997:Time Factors
chemical_list: D014150:Antipsychotic Agents; D007649:Ketamine; D008063:Thioctic Acid; D002746:Chlorpromazine
keywords: Chlorpromazine; Electroencephalogram; Hippocampus; Ketamine; Lipoic acid; Schizophrenia