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.