Olanzapine exposure diminishes perfusion and decreases volume of sensorimotor cortex in rats
| Autor: | Hana Kotolová, Zenon Starčuk, Katerina Horska, Zuzana Babinská, Eva Drazanova, Nadezda Vaskovicova, Radim Skoupy, Jana Ruda-Kucerova, Marcela Buchtová, Lucie Vrlíková, Lucie Krátká |
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| Rok vydání: | 2019 |
| Předmět: |
Olanzapine
medicine.medical_specialty medicine.drug_class Hippocampus Atypical antipsychotic Perfusion scanning Drug Administration Schedule Rats Sprague-Dawley 03 medical and health sciences 0302 clinical medicine Piriform cortex Internal medicine Cortex (anatomy) Animals Medicine Pharmacology Dose-Response Relationship Drug business.industry Organ Size General Medicine Magnetic Resonance Imaging 3. Good health medicine.anatomical_structure Endocrinology Isoflurane Cerebrovascular Circulation 030220 oncology & carcinogenesis Female Sensorimotor Cortex business Perfusion 030217 neurology & neurosurgery Antipsychotic Agents medicine.drug |
| Zdroj: | Pharmacological Reports. 71:839-847 |
| ISSN: | 1734-1140 |
| Popis: | Background Olanzapine is a frequently used atypical antipsychotic drug known to exert structural brain alterations in animals. This study investigated whether chronic olanzapine exposure alters regional blood brain perfusion assessed by Arterial Spin Labelling (ASL) magnetic resonance imaging (MRI) in a validated model of olanzapine-induced metabolic disturbances. An effect of acute olanzapine exposure on brain perfusion was also assessed for comparison. Methods Adult Sprague-Dawley female rats were treated by intramuscular depot olanzapine injections (100 mg/kg every 14 days) or vehicle for 8 weeks. ASL scanning was performed on a 9.4 T Bruker BioSpec 94/30USR scanner under isoflurane anesthesia. Serum samples were used to assay leptin and TNF-α level while brains were sliced for histology. Another group received only one non-depot intraperitoneal dose of olanzapine (7 mg/kg) during MRI scanning, thus exposing its acute effect on brain perfusion. Results Both acute and chronic dosing of olanzapine resulted in decreased perfusion in the sensorimotor cortex, while no effect was observed in the piriform cortex or hippocampus. Furthermore, in the chronically treated group decreased cortex volume was observed. Chronic olanzapine dosing led to increased body weight, adipose tissue mass and leptin level, confirming its expected metabolic effects. Conclusion This study demonstrates region-specific decreases in blood perfusion associated with olanzapine exposure present already after the first dose. These findings extend our understanding of olanzapine-induced functional and structural brain changes. |
| Databáze: | OpenAIRE |
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