Abstract
Schizophrenia, a disabling psychological disorder, is manifested by multifold pathophysiology. Abnormal membrane phospholipid metabolism related to abnormal essential polyunsaturated fatty acid (EPUFA) metabolism has also reported in recent studies. Antipsychotic drugs are effective in symptom control in up to two-thirds of patients, but in at least one-third of patients the response is poor often accompanied by side effects. Omega-3-fatty acids (OMG) are known to reverse lipid peroxidation. The objective of the study was to evaluate the synergistic activity of OMG in combination with reduced dose (1.5 mg/kg) risperidone (RISP) in ameliorating symptoms in rat model.Male Wistar rats were injected with Amphetamine (5 mg/kg) to induce schizophrenia-like symptoms. Following induction, the rats were administered intraperitoneal risperidone (3mg/kg), oral omega-3-fatty acids (EPA: DHA, 180:120) and combination of risperidone (1.5mg/kg) and Omega-3-fatty acids (EPA:DHA, 180:120) over 21 days. Two behavior models - motor coordination (Rota rod test) and catalepsy (catalepsy test) - were used to evaluate the schizophrenic behavior of the animals. Lipid profiles and schizophrenic symptoms were evaluated on Days 7 and 21, while antioxidant levels and dopamine levels in the rat brain were measured on Day 21 using spectrofluorimeter. On Day 21, brain dopamine decreased significantly in AMP+RISP and AMP+RISP+ OMG (p<0.01 for both) compared to AMP group, while no significant change was observed AMP+OMG group. Latency time increased significantly from baseline to Day 21 in AMP+RISP group , AMP+OMG group and AMP+RISP+OMG group compared to AMP (p<0.01). The total cholesterol and LDL-C levels decreased significantly from baseline to Day 21 in AMP+OMG and AMP+RISP+OMG groups (p<0.05 for both) compared to AMP. Our findings suggest that in schizophrenic rats, Omega-3-fatty acids co-administered with the reduced dose of risperidone provide beneficial effect to improve the diseased state. A lower dose seems to avoid side effects caused by long-term treatment with high dose of risperidone.
