Acute and chronic treatment with quetiapine induces antidepressant-like behavior and exerts antioxidant effects in the rat brain

Abstract

Many studies note that changes in oxidative balance are involved in the pathogenesis of major depressive disorder (MDD) and in the success of some antidepressants. Quetiapine exerts a therapeutic response and induces changes in physiological mechanisms that appear to underlie MDD. The objective of this study was to evaluate the antidepressant and antioxidant effects of quetiapine (20 mg /kg) in adult animals. Sixty minutes after an acute treatment or the last administration of chronic treatment (14 days) with quetiapine, animals were subjected to the forced swimming test (FST) to evaluate mobility parameters. Then, the hippocampus, prefrontal cortex (CPF), amygdala and nucleus accumbens (NAc) were removed for the assessment of oxidative stress parameters. Both acute and chronic treatments exerted antidepressant-like effects. Myeloperoxidase (MPO) activity was reduced in the amygdala after acute treatment and in the hippocampus, PFC and amygdala after chronic treatment. In addition, after chronic treatment, the levels of thiobarbituric reactive species (TBARS) were reduced in the amygdala and NAc, and the protein carbonyl content was reduced in the CPF. Superoxide dismutase (SOD) activity increased in the NAc after acute and chronic treatments. Catalase (CAT) activity increased in the PFC after acute treatment and in the NAc after acute and chronic treatments. The concentration of nitrite/nitrate was lower in the CPF after chronic treatment. These results corroborate the antidepressant effect of quetiapine and indicate that quetiapine exhibits an antioxidant profile, a physiological mechanism that appears be involved in the therapeutic function of quetiapine in individuals resistant to classical antidepressant treatments.

Neuroprotective potential of solanesol in intracerebroventricular propionic acid induced experimental model of autism: Insights from behavioral and biochemical evidence

“…The detection wavelength was 254 nm and the reference solution of ATP prepared according to the dissolving standard. Results expressed as nM/mg protein [71].…”

Effects of venlafaxine on the expression level and methylation status of genes involved in oxidative stress in rats exposed to a chronic mild stress

“…34,35 Interestingly, next study showed that the antidepressant therapy caused a reduction myeloperoxidase activity in the amygdala, hippocampus, amygdala and prefrontal cortex while SOD and CAT activity is believed to increase in nucleus accumbens of rat brain after antidepressant therapy. 36 Another important oxidative enzyme associated with depression is xanthine oxidase (XO); a post-mortem study had shown an increased level of XO in serum and the thalamus. 37,38 In addition, patients with depression have been characterized by decreased levels of vitamin E, vitamin C, zinc, uric acid, coenzyme Q10 and glutathione (GSH), although the latter did not change following electroconvulsive therapy.…”

“…Interestingly, we found that administration of venlafaxine to stressed animals significantly elevated the level of CAT protein in their midbrain and cerebral cortex. Similarly, catalase activity increased in the nucleus accumbens of rat brains after administration of quetiapine, an atypical antipsychotic used also in the pharmacotherapy of depression 36. In addition, a study employing a model of behavioural despair in mice showed that venlafaxine restored reduced CAT activity in the brain 41.…”

Putative neuroprotective pharmacotherapies to target the staged progression of mental illness

“…Quetiapine may also be an effective antioxidant. Across two studies in mice, acute and chronic quetiapine increased mitochondrial respiratory chain activity and reduced markers of oxidative stress in the prefrontal cortex, nucleus accumbens, amygdala and hippocampus (Ignacio et al, ; Ignácio et al, ).…”