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Permanent deficits in serotonergic functioning of olfactory bulbectomized rats: an in vivo microdialysis study
Hiske M van der Stelt1, Megan E Breuer, Berend Olivier
1Rudolf Magnus Institute of Neuroscience, Department of Psychiatry, University Medical Center Utrecht, The Netherlands.
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.
Insights
Olfactory bulbectomy in rats significantly alters serotonin levels and synthesis, leading to long-lasting hyperactivity. This makes it a valuable model for studying mood disorders.
Area of Science:
- Neuroscience
- Neuropharmacology
- Behavioral Science
Background:
- Bilateral olfactory bulbectomy (OBX) in rats mimics alterations seen in major depressive disorder (MDD).
- Serotonin's role in OBX mechanisms is of significant interest.
- Direct microdialysis measurement of serotonergic function in OBX animals was previously unreported.
Purpose of the Study:
- To investigate the effects of OBX on the functioning of the serotonergic system in rats.
- To assess changes in serotonin levels, synthesis, and release post-OBX.
- To evaluate behavioral alterations, specifically hyperactivity, in OBX rats.
Main Methods:
- In vivo microdialysis in conscious rats following OBX or sham surgery.
- Assessment of serotonergic system function via administration of fluvoxamine, fenfluramine, and NSD-1015.
- Open field testing to evaluate animal behavior and activity levels.
Main Results:
- OBX decreased basal extracellular serotonin (5-HT) levels in the amygdala and hippocampus.
- OBX reduced the rate of 5-HT synthesis but not its overall capacity.
- OBX rats exhibited persistent hyperactivity in the open field test.
Conclusions:
- OBX induces profound, long-lasting changes in serotonergic function and activity levels in rats.
- The OBX rat is a promising animal model for studying affective disorders.
- Microdialysis provides direct evidence of OBX-induced serotonergic system alterations.
