Olanzapine exposure diminishes perfusion and decreases volume of sensorimotor cortex in rats.
Animals
Antipsychotic Agents
/ administration & dosage
Cerebrovascular Circulation
/ drug effects
Dose-Response Relationship, Drug
Drug Administration Schedule
Female
Magnetic Resonance Imaging
Olanzapine
/ administration & dosage
Organ Size
/ drug effects
Rats, Sprague-Dawley
Sensorimotor Cortex
/ blood supply
Arterial spin labelling
Cortex
Leptin
Olanzapine
Sprague-Dawley rats
Journal
Pharmacological reports : PR
ISSN: 2299-5684
Titre abrégé: Pharmacol Rep
Pays: Switzerland
ID NLM: 101234999
Informations de publication
Date de publication:
Oct 2019
Oct 2019
Historique:
received:
31
01
2019
revised:
24
04
2019
accepted:
29
04
2019
pubmed:
9
8
2019
medline:
1
5
2020
entrez:
9
8
2019
Statut:
ppublish
Résumé
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. 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. 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. 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.
Sections du résumé
BACKGROUND
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
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
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
CONCLUSIONS
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.
Identifiants
pubmed: 31394417
pii: S1734-1140(19)30071-4
doi: 10.1016/j.pharep.2019.04.020
pii:
doi:
Substances chimiques
Antipsychotic Agents
0
Olanzapine
N7U69T4SZR
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
839-847Informations de copyright
Copyright © 2019 Institute of Pharmacology, Polish Academy of Sciences. Published by Elsevier B.V. All rights reserved.