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.

• MeSH
• antipsychotika aplikace a dávkování   škodlivé účinky   MeSH
• magnetická rezonanční tomografie MeSH
• mozkový krevní oběh účinky léků   MeSH
• olanzapin aplikace a dávkování   škodlivé účinky   MeSH
• potkani Sprague-Dawley MeSH
• rozvrh dávkování léků MeSH
• senzorimotorický kortex krevní zásobení   diagnostické zobrazování   účinky léků   MeSH
• velikost orgánu účinky léků   MeSH
• vztah mezi dávkou a účinkem léčiva MeSH
• zvířata MeSH
• Check Tag
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH

Clinical studies consistently report structural impairments (i.e.: ventricular enlargement, decreased volume of anterior cingulate cortex or hippocampus) and functional abnormalities including changes in regional cerebral blood flow in individuals suffering from schizophrenia, which can be evaluated by magnetic resonance imaging (MRI) techniques. The aim of this study was to assess cerebral blood perfusion in several schizophrenia-related brain regions using Arterial Spin Labelling MRI (ASL MRI, 9.4 T Bruker BioSpec 94/30USR scanner) in rats. In this study, prenatal exposure to methylazoxymethanol acetate (MAM, 22 mg/kg) at gestational day (GD) 17 and the perinatal treatment with Δ-9-tetrahydrocannabinol (THC, 5 mg/kg) from GD15 to postnatal day 9 elicited behavioral deficits consistent with schizophrenia-like phenotype, which is in agreement with the neurodevelopmental hypothesis of schizophrenia. In MAM exposed rats a significant enlargement of lateral ventricles and perfusion changes (i.e.: increased blood perfusion in the circle of Willis and sensorimotor cortex and decreased perfusion in hippocampus) were detected. On the other hand, the THC perinatally exposed rats did not show differences in the cerebral blood perfusion in any region of interest. These results suggest that although both pre/perinatal insults showed some of the schizophrenia-like deficits, these are not strictly related to distinct hemodynamic features.

• MeSH
• circulus arteriosus Willisi diagnostické zobrazování   účinky léků   embryologie   MeSH
• hipokampus krevní zásobení   diagnostické zobrazování   účinky léků   embryologie   MeSH
• krysa rodu rattus MeSH
• lidé MeSH
• magnetická rezonanční angiografie metody   MeSH
• methylazoxymethanolacetát toxicita   MeSH
• modely nemocí na zvířatech MeSH
• mozkový krevní oběh účinky léků   MeSH
• neurogeneze účinky léků   MeSH
• schizofrenie chemicky indukované   diagnóza   MeSH
• senzorimotorický kortex krevní zásobení   diagnostické zobrazování   účinky léků   embryologie   MeSH
• techniky pozorování chování MeSH
• těhotenství MeSH
• tetrahydrokanabinol toxicita   MeSH
• zpožděný efekt prenatální expozice chemicky indukované   diagnostické zobrazování   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu rattus MeSH
• lidé MeSH
• mužské pohlaví MeSH
• těhotenství MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH