Olanzapine exposure diminishes perfusion and decreases volume of sensorimotor cortex in rats
Language English Country Switzerland Media print-electronic
Document type Journal Article
PubMed
31394417
DOI
10.1016/j.pharep.2019.04.020
PII: S1734-1140(19)30071-4
Knihovny.cz E-resources
- Keywords
- Arterial spin labelling, Cortex, Leptin, Olanzapine, Sprague-Dawley rats,
- MeSH
- Antipsychotic Agents administration & dosage adverse effects MeSH
- Magnetic Resonance Imaging MeSH
- Cerebrovascular Circulation drug effects MeSH
- Olanzapine administration & dosage adverse effects MeSH
- Rats, Sprague-Dawley MeSH
- Drug Administration Schedule MeSH
- Sensorimotor Cortex blood supply diagnostic imaging drug effects MeSH
- Organ Size drug effects MeSH
- Dose-Response Relationship, Drug MeSH
- Animals MeSH
- Check Tag
- Female MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Names of Substances
- Antipsychotic Agents MeSH
- Olanzapine MeSH
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.
Department of Pharmacology Faculty of Medicine Masaryk University Brno Czech Republic
Institute of Scientific Instruments of the Czech Academy of Sciences Brno Czech Republic
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