Abstract
The use of atypical antipsychotic drugs like olanzapine is associated with side effects such as sedation and depression-like symptoms, especially during the initial period of the use. It is believed that the occurrence of these undesirable effectsis mainly the result of the histamine H1receptors blockade by olanzapine. In addition, use of olanzapine increases the level of triglycerides in the blood, which correlates with growing obesity. The aim of this study was to investigate the influence of pitolisant – H3 histamine antagonist - on subchronic olanzapine-induced depresion-like symptoms, sedation and hypertriglicerydemia. Forced swim test was conducted to determinate depressive-like effect of olanzapine and antidepressive-like activity during the co-administered pitolisant. The test was performed after the first and fifteenth day of the treatment of the mice. The spontaneous activity of the mice was measured on the fourteenth day of the treatment with a special, innovative RFID-system (Radio-frequency identification system) – TraffiCage (TSE-Systems, Germany). Triglyceride levels were determined on the sixteenth day of the experiment after 15 cycles of drug administration. Daily olanzapine treatment (4 mg/kg b.w., i.p., d.p.d) for 15 days significantly induces sedation (p < 0.05) and prolongs immobility time in forced swim tests (FST) in mice (p < 0.05); and also elevates the level of triglycerides (p < 0.05). Administration of pitolisant (10 mg/kg b.w., i.p.) subsequentto olanzapine normalizes these adverse effects. This study presents a promising alternative for counteracting some behavioral changes and metabolic disturbances which occur in the early period of treatment with antipsychotic drugs.
Highlights
Olanzapine is one of the most commonly used atypical drugs for schizophrenia (Podogrodzka and Jarema 2010), and one of the strongest antagonists of the H1 histamine receptors (H1R) (Richelson and Souder 2000)
This study presents a promising alternative for counteracting some behavioral changes and metabolic disturbances which occur in the early period of treatment with antipsychotic drugs
Atypical antipsychotics such as olanzapine may increase the level of triglycerides in the blood (Albaugh et al 2011; Misiak et al 2014), which correlates with the development of obesity during the treatment
Summary
Olanzapine is one of the most commonly used atypical drugs for schizophrenia (Podogrodzka and Jarema 2010), and one of the strongest antagonists of the H1 histamine receptors (H1R) (Richelson and Souder 2000). The use of atypical antipsychotic drugs like olanzapine is associated with some side effects, such as sedation and depression-like symptoms, especially in the initial period of the use (Podogrodzka and Jarema 2010). Atypical antipsychotics such as olanzapine may increase the level of triglycerides in the blood (Albaugh et al 2011; Misiak et al 2014), which correlates with the development of obesity during the treatment. It is believed that the occurrence of these undesirable effects may be
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