title: H3 histamine receptor antagonist pitolisant reverses some subchronic disturbances induced by olanzapine in mice.
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.
authors.affiliation: Department of Pharmacodynamics, Jagiellonian University Medical College, 9 Medyczna Street, 30-688, Krakow, PL, Poland. magda.dudek@uj.edu.pl.
authors.forename: Magdalena
authors.initials: M
authors.lastname: Dudek
authors.affiliation: Department of Technology and Biotechnology of Drugs, Faculty of Pharmacy, Jagiellonian University Medical College, Krakow, Poland.
authors.forename: Kamil
authors.initials: K
authors.lastname: Kuder
authors.affiliation: Chair of Pharmaceutical Chemistry, Faculty of Pharmacy, Jagiellonian University Medical College, Medyczna 9, 30-688, Krakow, Poland.
authors.forename: Marcin
authors.initials: M
authors.lastname: Kołaczkowski
authors.affiliation: Institute of Automatic Control, Silesian University of Technology, Gliwice, Poland.
authors.forename: Adrian
authors.initials: A
authors.lastname: Olczyk
authors.affiliation: Department of Pharmacological Screening, Jagiellonian University Medical College, 9 Medyczna Street, 30-688, Krakow, PL, Poland.
authors.forename: Elżbieta
authors.initials: E
authors.lastname: Żmudzka
authors.affiliation: Department of Pharmacological Screening, Jagiellonian University Medical College, 9 Medyczna Street, 30-688, Krakow, PL, Poland.
authors.forename: Aleksandra
authors.initials: A
authors.lastname: Rak
authors.affiliation: Department of Pharmacological Screening, Jagiellonian University Medical College, 9 Medyczna Street, 30-688, Krakow, PL, Poland.
authors.forename: Marek
authors.initials: M
authors.lastname: Bednarski
authors.affiliation: Department of Pharmacodynamics, Jagiellonian University Medical College, 9 Medyczna Street, 30-688, Krakow, PL, Poland.
authors.forename: Karolina
authors.initials: K
authors.lastname: Pytka
authors.affiliation: Department of Pharmacological Screening, Jagiellonian University Medical College, 9 Medyczna Street, 30-688, Krakow, PL, Poland.
authors.forename: Jacek
authors.initials: J
authors.lastname: Sapa
authors.affiliation: Department of Technology and Biotechnology of Drugs, Faculty of Pharmacy, Jagiellonian University Medical College, Krakow, Poland.
authors.forename: Katarzyna
authors.initials: K
authors.lastname: Kieć-Kononowicz
mesh_terms: D000818:Animals; D014150:Antipsychotic Agents / Q000008:administration & dosage* / Q000633:toxicity; D001569:Benzodiazepines / Q000008:administration & dosage* / Q000633:toxicity; D003863:Depression / Q000139:chemically induced / Q000188:drug therapy / Q000523:psychology; D004305:Dose-Response Relationship, Drug; D005260:Female; D054828:Histamine H3 Antagonists / Q000494:pharmacology* / Q000627:therapeutic use; D008124:Locomotion / Q000187:drug effects / Q000502:physiology*; D051379:Mice; D000077152:Olanzapine; D010880:Piperidines / Q000494:pharmacology* / Q000627:therapeutic use; D018100:Receptors, Histamine H3 / Q000502:physiology*
chemical_list: D014150:Antipsychotic Agents; D054828:Histamine H3 Antagonists; D010880:Piperidines; D018100:Receptors, Histamine H3; D001569:Benzodiazepines; C516975:pitolisant; D000077152:Olanzapine
keywords: Depression-like symptoms; Locomotor activity; Olanzapine; Pitolisant; Sedation; Triglycerides