The antipsychotic effect of omega-3 fatty acids in rats

Objective: Even though oxidative stress is not the main reason of schizophrenia, it is accepted as having an important role in pathophysiology of schizophrenia. Oxidative products with their effects to cell membrane proteins can cause deterioration in functions of enzymes, neurotransmitters, receptor proteins, and it can break down integrity by reducing cell membrane permeability and şuidity. In human beings omega-3 fatty acids is necessary for cell membranes, brain functions and continuation of nerve transmission. When the animals are exposed to a new environment or an agent like apomorphine that makes an agonistic effect to D1 and D2 receptors is administered, the animals display rearing behavior and behavioral reactions like stereotypy. These reactions are arranged by multiple neurotransmitter system that includes many neurotransmitters like GABA A, opioid, and Dopamine D2 receptors. In these locomotor activity and stereotypic behaviors, mesolimbic and nigrostriatal dopaminergic pathways have a crucial role.

Method: 28 adult male Wistar rats (220–240 g) were used in the study. Novelty- induced rearing behavior is used to assess the central excitatory locomotor behavior in rodents. Four groups of rat (n=7) were administered Docosahexaenoic acid (DHA)+eicosapentaenoic acid (EPA) (300 mg/kg; DHA: 120 mg/kg + EPA: 180 mg/kg i.p.), DHA+EPA (150 mg/kg; DHA: 60 mg/kg + EPA: 90 mg/kg ip.), chlorpromazine (1 mg/kg; ip.), or isotonic NaCl (1 mL/kg, ip.). The rearing frequency was recorded for 10 min. Apomorphine-induced stereotypy is due to the stimulation of dopamine receptors and has been used as a convenient method for in vivo screening of dopamine agonists or antagonists and assessment of dopaminergic activity. Brieşy, four groups of rat (n=7) were administered DHA+EPA (300 mg/kg; DHA: 120 mg/kg + EPA: 180 mg/kg ip.), DHA+EPA (150 mg/kg; DHA: 60 mg/kg + EPA: 90 mg/kg ip.), chlorpromazine (1 mg/kg, ip.), and isotonic saline (1 mL/kg, ip.). One hour later, apomorphine (2 mg/kg, sc.) was administered to each rat. After apomorphine administration, rats observed for stereotypy behavior. The stereotypy behavior was rated after each minute, and mean of 15 min period was calculated and recorded. Brain tissue malondialdehyde (MDA) and glutathione (GSH) levels were measured in each group.

Results: DHA+EPA (150 mg/kg), DHA+EPA (300 mg/kg) and chlorpromazine significantly decrease apomorphine induced stereotypy scores compared to control group (p<0.001). DHA+EPA (300 mg/kg) and chlorpromazine significantly decrease rearing behavior scores and brain MDA levels compared to control group (p<0.001). DHA+EPA (150 mg/kg) significantly decrease rearing behavior scores and brain MDA levels compared to control group (p<0.01). DHA+EPA (150 mg/kg) and chlorpromazine significantly increase brain GSH levels compared to control group (p<0.05). DHA+EPA (300 mg/kg) significantly increase brain GSH levels compared to control group (p<0.001).

Conclusion: In this study it is shown that, omega-3 fatty acids similar to antipsychotics, reversed the psychotic-like effects, increase of oxidants and decrease the level of antioxidants that are composed experimentally in rats. In conclusion, the application of omega-3 fatty acids are found to be having antipsychotic effect and arranging oxidative imbalance, and it is decided that omega-3 could be an alternative treatment that can provide the schizophrenic patients with additional benefit.