Chronic therapy with citalopram decreases regional cerebral glucose utilization in OBX, and not sham-operated, rats: an autoradiographic study

• Published in: Psychopharmacologia 2009-12, Vol.207 (2), p.315-323
• Main Authors: Skelin, Ivan, Sato, Hiroki, Kovačević, Tomislav, Diksic, Mirko
• Format: Article
• Language: English
• Subjects: Adult and adolescent clinical studies; Animals; Antidepressants; Autoradiography; Biological and medical sciences; Biomedical and Life Sciences; Biomedicine; Brain - metabolism; Citalopram - administration & dosage; Citalopram - pharmacology; Deoxyglucose - metabolism; Depression; Drug Administration Schedule; Infusion Pumps, Implantable; Linear Models; Male; Medical sciences; Mental depression; Mood disorders; Neuropharmacology; Neurosciences; Neurotransmitters; Olfactory Bulb - surgery; Original Investigation; Pharmacology. Drug treatments; Pharmacology/Toxicology; Psychiatry; Psychoanaleptics: cns stimulant, antidepressant agent, nootropic agent, mood stabilizer; Psychoanaleptics: cns stimulant, antidepressant agent, nootropic agent, mood stabilizer..., (alzheimer disease); Psychology. Psychoanalysis. Psychiatry; Psychopathology. Psychiatry; Psychopharmacology; Rats; Rats, Sprague-Dawley; Rodents; Serotonin Uptake Inhibitors - administration & dosage; Serotonin Uptake Inhibitors - pharmacology
• ISSN: 0033-3158; 1432-2072
• DOI: 10.1007/s00213-009-1659-4

Rationale Chronic treatment with the selective serotonin reuptake inhibitor, citalopram, normalizes several behavioral and neurochemical abnormalities in the olfactory bulbectomized (OBX) rat model of depression. Objective To assess the changes in regional cerebral glucose utilization (rCGU) following chronic treatment with citalopram in OBX and sham-operated rats. Methods Male Sprague Dawley rats (160–190 g) were used. Two weeks following the surgeries, the rats were implanted with osmotic minipumps which delivered 10 mg/kg/day of citalopram (the sham-CTP and OBX-CTP groups) or saline (to the sham-SAL and OBX-SAL groups) for 2 weeks. Following the treatment, the rates of rCGU were determined in 43 brain regions using 2-[ 14 C]deoxyglucose (2-[ 14 C]DG) autoradiography. Results The general linear model statistical analysis revealed significantly lower rCGU in the OBX-SAL group compared to the sham-SAL group in the medial prefrontal cortex and the median forebrain bundle. The sham-CTP group had significantly lower rCGU relative to the sham-SAL group in the medial prefrontal cortex. The OBX-CTP group had significantly lower rCGU than the OBX-SAL group in the anterior olfactory nucleus, orbitofrontal cortex, frontal cortex, anterior cingulate cortex, visual cortex, and substantia nigra—pars reticulata. The rCGU in the OBX-CTP group was significantly lower than that in the sham-CTP group in the anterior olfactory nucleus, orbitofrontal cortex, visual cortex, and substantia nigra—pars reticulata. Conclusion The results imply that chronic citalopram treatment, shown previously to result in behavioral normalization in OBX rats, establishes a new pattern of rCGU, rather than normalizing it to the pattern of the sham-CTP rats.