Chronic administration of citalopram in olfactory bulbectomy rats restores brain 5-HT synthesis rates: an autoradiographic study.
BACKGROUND
The olfactory bulbectomized (OBX) rat model is widely accepted as an animal model of depression with a proposed serotonergic imbalance in the brain.


OBJECTIVE
To study the effects of chronic administration of citalopram on serotonin (5-HT) synthesis rates.


METHODS
Serotonin synthesis was evaluated using the alpha-[(14)C]methyl-L: -tryptophan (alpha-MTrp) autoradiographic method in OBX rats. Citalopram was administered continuously (10 mg kg(-1) day(-1)) for 14 days using a subcutaneous osmotic minipump.


RESULTS
The OBX rats treated with citalopram (OBX-CTP) have the same 5-HT synthesis rates as the sham-operated rats treated with citalopram (Sham-CTP). The OBX-CTP rats, relative to the OBX rats treated with saline (OBX-SAL), showed a reduction in the majority of the terminal brain structures, suggesting a normalization of 5-HT synthesis in the OBX-CTP rats following treatment. The OBX-SAL rats have significantly greater synthesis than the Sham-SAL rats in a majority of the terminal structures, but lower rates in the dorsal raphe. A few structures in the OBX-CTP group have lower synthesis than in the Sham-SAL group (e.g., dorsal raphe, hippocampus, amygdala). The data suggest that receptors in some brain areas are likely still responsive to the elevated levels of the extracellular 5-HT produced by citalopram.


CONCLUSIONS
There is no significant global or individual structure difference in the synthesis between the Sham-CTP and OBX-CTP groups. The similarity in the synthesis between the OBX-CTP, Sham-CTP and Sham-SAL groups is likely a result of changes in the sensitivity of the receptors through which 5-HT synthesis is controlled. Because of some of the differences in the synthesis between the Sham-CTP and Sham-SAL groups, the data suggest that receptors throughout the brain are not fully desensitized.
Hasegawa
Shu
S
Cone Neurosurgical Research Laboratory, Department of Neurology and Neurosurgery, Montreal Neurological Institute, Montreal, Quebec, Canada.
Watanabe
Arata
A
Nguyen
Khanh Q
KQ
Debonnel
Guy
G
Diksic
Mirko
M
D000818:Animals; D001345:Autoradiography; D001923:Brain Chemistry / Q000187:drug effects*; D015283:Citalopram / Q000494:pharmacology*; D006400:Hematocrit; D007700:Kinetics; D008297:Male; D009830:Olfactory Bulb / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012701:Serotonin / Q000096:biosynthesis*; D017367:Selective Serotonin Reuptake Inhibitors / Q000494:pharmacology*; D014364:Tryptophan / Q000031:analogs & derivatives / Q000097:blood / Q000494:pharmacology
D015283:Citalopram; D012701:Serotonin; D017367:Selective Serotonin Reuptake Inhibitors; D014364:Tryptophan; C020774:alpha-methyltryptophan