Abstract
Background: The present study compares the efficacy of quetiapine fumarate (QF) and QF-loaded solid lipid nanoparticles (QFSLN) as antipsychotic drugs for schizophrenia. Methods: To induce schizophrenia-like symptoms, a group of rats was injected intraperitoneally (i.p.) with ketamine (25mg/kg b.w.) for 1 week to establish a rat model of schizophrenia. The incidence of schizophrenic symptoms was estimated to be equivalent to the control group. To estimate the pronounced antipsychotic effect of QF, a low dose (LD) of 10 mg/kg b.w. and a high dose (HD) of 30 mg /kg b.w. were orally administrated to two groups of rats (designated L.QF and H.QF) for 3 weeks (2 weeks without ketamine injection; the last week with ketamine). To achieve the optimal therapeutic response of QF drug, 2 other groups of rats were administered orally the equivalent low and high doses of QF in its solid lipid nanoparticle form (L.QFSLN) and (H.QFSLN) for 3 weeks in the same manner. The treatments were given after 1 h of ketamine injection. To assess the effect of different doses of treatment on hyperlocomotion and cognitive impairment induced by ketamine, an open field test and passive avoidance test were conducted. In addition, excitatory and inhibitory amino acids, as well as catecholamines, were estimated in brain regions (cortex and hippocampus). The study was extended to estimate the side effects of different treatments on hepatorenal functions and lipid profile. Additionally, samples were subjected to immunohistochemical analysis. Results: QFSLN treatment showed enhanced effect over QF in a dose-dependent manner with minimal side effects in schizophrenic rats. In addition, immunohistochemical examinations of brain tissues confirmed the biochemical data.
Highlights
Schizophrenia is a complex neuropsychiatric disease that consists of positive symptoms, negative symptoms, and cognitive impairments (Pickard, 2015)
The number of squares in the open field test were significantly increased (p
These effects were more pronounced (p
Summary
Schizophrenia is a complex neuropsychiatric disease that consists of positive symptoms (delusions and hallucinations), negative symptoms (blunted affect and social withdrawal), and cognitive impairments (Pickard, 2015). The scientific evidence of the involvement of glutamate is from the fact that phencyclidine (PCP) and ketamine are two N-methyl-D-aspartate (NMDA) glutamatergic receptor antagonist drugs which cause severe symptoms similar to those observed in schizophrenia (Arion et al, 2007; De Oliveira et al, 2011). To estimate the pronounced antipsychotic effect of QF, a low dose (LD) of 10 mg/kg b.w. and a high dose (HD) of 30 mg /kg b.w. were orally administrated to two groups of rats (designated L.QF and H.QF) for 3 weeks (2 weeks without ketamine injection; the last week with ketamine). To achieve the optimal therapeutic response of QF drug, 2 other groups of rats were administered orally the equivalent low and high doses of QF in its solid lipid nanoparticle form (L.QFSLN) and (H.QFSLN) for 3 weeks in the same manner. Immunohistochemical examinations of brain tissues confirmed the biochemical data
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