ABSTRACT
Supplementation with omega-3 has been identified as an adjunctive alternative for the treatment of psychiatric disorders, in order to minimize symptoms. Considering the lack of understanding concerning the pathophysiology of schizophrenia, the present study hypothesized that omega 3 prevents the onset of symptoms similar to schizophrenia in young Wistar rats submitted to ketamine treatment. Moreover, the role of oxidative stress in this model was assessed. Omega-3 (0.8g/kg) or vehicle was given by orogastric gavage once daily. Both treatments were performed during 21days, starting at the 30th day of life in young rats. After 14days of treatment with omega-3 or vehicle, a concomitant treatment with saline or ketamine (25mg/kg ip daily) was started and maintained until the last day of the experiment. We evaluated the pre-pulse inhibition of the startle reflex, activity of antioxidant systems and damage to proteins and lipids. Our results demonstrate that supplementation of omega-3 prevented: decreased inhibition of startle reflex, damage to lipids in the hippocampus and striatum and damage to proteins in the prefrontal cortex. Furthermore, these changes are associated with decreased GPx in brain tissues evaluated. Together, our results suggest the prophylactic role of omega-3 against the outcome of symptoms associated with schizophrenia.
Subject(s)
Brain Injuries/diet therapy , Brain Injuries/etiology , Fatty Acids, Omega-3/administration & dosage , Mental Disorders/prevention & control , Schizophrenia/complications , Animals , Brain/drug effects , Brain/metabolism , Disease Models, Animal , Dose-Response Relationship, Drug , Glutathione Peroxidase/metabolism , Ketamine/toxicity , Male , Malondialdehyde/metabolism , Mental Disorders/etiology , Oxidative Stress/drug effects , Protein Carbonylation/drug effects , Rats , Rats, Wistar , Schizophrenia/chemically induced , Schizophrenia/pathology , Sensory Gating/drug effects , Superoxide Dismutase/metabolism , Thiobarbituric Acid Reactive Substances/metabolismABSTRACT
Maternal deprivation has been associated with physiological and developmental changes that may be related to an increased risk for childhood and adult neuropsychiatric diseases. A growing number of studies demonstrated the importance of childhood experiences in the development of psychosis and schizophrenia in adulthood. Therefore, the present study investigated different behavior responses in rats following maternal deprivation and/or ketamine treatment in adulthood. Male rats were subjected to maternal deprivation for 180 min from postnatal day-01 to postnatal day-10. We evaluated locomotor activity, avoidance task and social interaction of adult male rats deprived or not deprived that were administered with saline or acute subanesthetic doses of ketamine (5, 15 and 25 mg/kg, i.p.). Our results show that only ketamine (25 mg/kg, i.p.) treatment in the adult rats lead to hyperlocomotion but not ketamine (5 and 15 mg/kg) and maternal deprivation alone. However, maternally deprived rats treated with ketamine (5 mg/kg) induced hyperlocomotion. Additionally, ketamine (25 mg/kg) and maternal deprivation alone induced cognitive deficit in the avoidance task. Rats deprived of and treated with ketamine (5, 15 and 25 mg/kg) also lead to memory deficit. Moreover, ketamine (25 mg/kg) and maternal deprivation alone increased latency to start social behavior. However, ketamine (5 mg/kg) and maternal deprivation lead to an increase of latency to start social behavior. Biochemistry data showed that all doses of ketamine and ketamine plus maternal deprivation increased the acetylcholinesterase (AChE) activity in the prefrontal cortex, hippocampus and striatum. The major doses of ketamine associated with maternal deprivation induced a major increase of AChE activity. Together, our results suggest that animals subjected to maternal deprivation had an increased risk for schizophrenia-like behavior and cholinergic alteration.
Subject(s)
Acetylcholinesterase/metabolism , Aging/psychology , Behavior, Animal , Maternal Deprivation , Schizophrenia/metabolism , Schizophrenic Psychology , Animals , Avoidance Learning , Disease Models, Animal , Ketamine/toxicity , Locomotion , Male , Memory , Motor Activity , Rats , Schizophrenia/chemically induced , Social BehaviorABSTRACT
The concept of developmental origins of health and disease has been defined as the process through which the environment encountered before birth, or in infancy, shapes the long-term control of tissue physiology and homeostasis. The evidence for programming derives from a large number of experimental and epidemiological observations. Several nutritional interventions during diverse phases of pregnancy and lactation in rodents are associated with fetal and neonatal programming for metabolic syndrome. In this paper, recent experimental models and human epidemiological studies providing evidence for the fetal programming associated with the development of metabolic syndrome and related diseases are revisited.
