Permanent deficits in serotonergic functioning of olfactory bulbectomized rats: an in vivo microdialysis study.
BACKGROUND
Bilateral removal of the olfactory bulbs (OBX) in rats results in a complex constellation of behavioral, neurochemical, neuroendocrine, and neuroimmune alterations, many of which are also reported in patients with major depressive disorder (MDD). Drawing on clinical findings, there has been considerable interest in the role of serotonin in the mechanism of action of OBX. However, to date, there has been no report of direct measurement of serotonergic functioning of bulbectomized animals using microdialysis. The present study describes the effects of olfactory bulbectomy on functioning of the serotonergic system.


METHODS
In vivo microdialysis was performed in conscious rats that underwent OBX or sham surgery. Alterations in the functioning of the serotonergic system were assessed by administration of fluvoxamine, fenfluramine, and 3-hydroxybenzylhydrazine (NSD-1015). Animals were also repeatedly tested in an open field.


RESULTS
Bilateral removal of the olfactory bulbs decreased basal extracellular levels by decreasing the releasable pool of serotonin (5-HT) in the basolateral amygdala 2 weeks after surgery and in the dorsal hippocampus 2 weeks and 5 months after surgery. Olfactory bulbectomized animals showed a lower rate of 5-HT synthesis under basal conditions. However, the capacity of the system to synthesize 5-HT was not affected. Olfactory bulbectomized rats were hyperactive in the open field. This hyperactivity remained after successive testing, indicating permanent behavioral changes.


CONCLUSIONS
This microdialysis study shows that OBX has profound and long-lasting effects on serotonergic functioning and on activity levels and is therefore considered an intriguing and promising animal model for affective processes in the brain.
van der Stelt
Hiske M
HM
Rudolf Magnus Institute of Neuroscience, Department of Psychiatry, University Medical Center Utrecht, The Netherlands.
Breuer
Megan E
ME
Olivier
Berend
B
Westenberg
Herman G M
HG
D000818:Animals; D019540:Area Under Curve; D001522:Behavior, Animal; D001835:Body Weight / Q000502:physiology; D001921:Brain / Q000033:anatomy & histology / Q000378:metabolism; D001923:Brain Chemistry; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D004298:Dopamine / Q000378:metabolism; D004563:Electrochemistry / Q000379:methods; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005106:Exploratory Behavior / Q000502:physiology; D005277:Fenfluramine / Q000494:pharmacology; D016666:Fluvoxamine / Q000494:pharmacology; D006834:Hydrazines / Q000494:pharmacology; D006897:Hydroxyindoleacetic Acid / Q000378:metabolism; D008297:Male; D017551:Microdialysis; D015999:Multivariate Analysis; D000857:Olfaction Disorders / Q000378:metabolism* / Q000503:physiopathology; D009830:Olfactory Bulb / Q000187:drug effects / Q000502:physiology* / Q000601:surgery*; D009833:Olfactory Pathways / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012701:Serotonin / Q000378:metabolism*; D017367:Selective Serotonin Reuptake Inhibitors / Q000494:pharmacology; D013997:Time Factors
D004298:Dopamine; D004791:Enzyme Inhibitors; D005277:Fenfluramine; D016666:Fluvoxamine; D006834:Hydrazines; D006897:Hydroxyindoleacetic Acid; D012701:Serotonin; D017367:Selective Serotonin Reuptake Inhibitors; C004297:3-hydroxybenzylhydrazine