title: Celecoxib and omega-3 fatty acids alone and in combination with risperidone affect the behavior and brain biochemistry in amphetamine-induced model of schizophrenia.
abstract: The implications of oxidative stress and neuro-inflammation in the pathogenesis of schizophrenia have been elucidated. Despite their effectiveness against positive symptoms of schizophrenia, antipsychotics have limited effectiveness against negative and cognitive symptoms and are associated with remarkable adverse effects. The use of celecoxib or omega-3 in schizophrenia may have beneficial effects. This study aimed to evaluate the possible efficacies of celecoxib, omega-3 or the combination of celecoxib+risperidone and omega-3+ risperidone compared to risperidone on the behavior and brain biochemistry in rats. In the present study, an amphetamine-induced model of schizophrenia in adult male rats was used to evaluate the effects of celecoxib, omega-3, celecoxib+risperidone and omega-3+ risperidone on the behavior of animals and on brain lipid peroxidation or tumor necrosis factor-alpha. In the water maze task, celecoxib, omega-3, celecoxib+risperidone, omega-3+ risperidone significantly decreased the latency time compared to amphetamine-treated group. Celecoxib, omega-3, celecoxib+risperidone, omega-3+risperidone also significantly reversed the decreased spontaneous alternation induced by amphetamine in the Y-maze task. In the social interaction task, groups treated with celecoxib, omega-3, celecoxib+risperidone, omega-3+ risperidone spent less time to recognize foreign animals than animals in the amphetamine-treated group. Increased brain MDA and TNF-α levels due to amphetamine were significantly reduced in groups treated with celecoxib+risperidone or omega-3+ risperidone. The present findings showed that celecoxib or omega-3 can attenuate amphetamine- induced behavioral impairment and these effects may be associated with their ability to decrease lipid peroxidation and cytokine release. Celecoxib or omega-3 may be promising candidates as adjuvant therapy for schizophrenia.
authors.affiliation: Department of Pharmacology and Toxicology, Faculty of Pharmacy, Tanta University, Egypt.
authors.forename: Alaa
authors.initials: A
authors.lastname: El-Sayed El-Sisi
authors.affiliation: Department of Pharmacology and Toxicology, Faculty of Pharmacy, Tanta University, Egypt.
authors.forename: Samia Salem
authors.initials: SS
authors.lastname: Sokkar
authors.affiliation: Department of Pharmacology and Toxicology, Faculty of Pharmacy, Tanta University, Egypt.
authors.forename: Magda
authors.initials: M
authors.lastname: El-Sayed El-Sayad
authors.affiliation: Department of Neuropsychiatry, Faculty of Medicine, University of Tanta, Egypt.
authors.forename: Ehab
authors.initials: E
authors.lastname: Sayed Ramadan
authors.affiliation: Department of Pharmacology and Toxicology, Faculty of Pharmacy, Tanta University, Egypt. Electronic address: enassyoussefosman@yahoo.com.
authors.forename: Enass Yossef
authors.initials: EY
authors.lastname: Osman
mesh_terms: D000661:Amphetamine; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D000068579:Celecoxib / Q000494:pharmacology / Q000627:therapeutic use*; D004195:Disease Models, Animal; D004359:Drug Therapy, Combination; D015525:Fatty Acids, Omega-3 / Q000494:pharmacology / Q000627:therapeutic use*; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D018782:Maze Learning / Q000187:drug effects; D051381:Rats; D018967:Risperidone / Q000494:pharmacology / Q000627:therapeutic use*; D012559:Schizophrenia / Q000139:chemically induced* / Q000188:drug therapy*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D015525:Fatty Acids, Omega-3; D014409:Tumor Necrosis Factor-alpha; D008315:Malondialdehyde; D000661:Amphetamine; D000068579:Celecoxib; D018967:Risperidone
keywords: Celecoxib; Neuro-inflammation; Omega-3 fatty acids; Oxidative stress; Schizophrenia