Chronic buspirone treatment decreases 5-HT1B receptor densities and the serotonin transporter but increases the density of 5-HT2A receptors in the bulbectomized rat model of depression: an autoradiographic study.
The olfactory bulbectomized (OBX) rat model is an animal model of depression. The deregulation of the serotonergic (5-HT) system is implicated in the pathophysiology of depression. Buspirone is a partial agonist of 5-HT(1A) receptors and is used in the treatment of depression and anxiety. The aim of this study was to assess, in OBX rats and sham operated controls, the effect of chronic buspirone treatment on the densities of 5-HT(2A) and 5-HT(1B) receptors, as well as the 5-HT transporter (5-HTT), which are all important mediators of 5-HT transmission. Male Sprague-Dawley rats (180-240 g) were used. Two weeks following the surgeries, the rats were assigned into the saline or treatment groups, receiving either saline, or 10 or 20 mg/kg day of buspirone, for 2 weeks by subcutaneous mini pump. Following the treatment, the rats were sacrificed. The autoradiographic experiments were performed ex vivo using [(3)H]5-HT for the 5-HT(1B) receptors, [(3)H]-ketanserin for the 5-HT(2A) receptors, and [(3)H]-paroxetine for the 5-HTT binding. The receptors and 5-HTT densities were quantified in 38 brain regions as well as the pineal body. Chronic treatment with buspirone produced the following: 1) a decrease in the 5-HT(1B) densities, which was more pronounced in the Sham rats; 2) an increase in the 5-HT(2A) receptor densities, which was more pronounced in the Sham rats; and 3) an decrease in 5-HTT densities in both groups. The results indicate differential effects of chronic antidepressant treatment on the 5-HT system regulation in the OBX model of depression and normal rats.
Sato
Hiroki
H
Department of Neurology and Neurosurgery, McGill University, Montreal, Quebec, Canada.
Skelin
Ivan
I
Diksic
Mirko
M
D000818:Animals; D001345:Autoradiography; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D002065:Buspirone / Q000008:administration & dosage / Q000494:pharmacology*; D003866:Depressive Disorder / Q000188:drug therapy* / Q000378:metabolism; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D015918:Infusion Pumps, Implantable; D008297:Male; D009830:Olfactory Bulb / Q000293:injuries; D010870:Pineal Gland / Q000187:drug effects / Q000378:metabolism; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D044302:Receptor, Serotonin, 5-HT1B / Q000378:metabolism*; D044402:Receptor, Serotonin, 5-HT2A / Q000378:metabolism*; D058826:Serotonin 5-HT2 Receptor Agonists; D050486:Serotonin Plasma Membrane Transport Proteins / Q000378:metabolism*; D017366:Serotonin Receptor Agonists / Q000008:administration & dosage / Q000494:pharmacology*; D013997:Time Factors
D044302:Receptor, Serotonin, 5-HT1B; D044402:Receptor, Serotonin, 5-HT2A; D058826:Serotonin 5-HT2 Receptor Agonists; D050486:Serotonin Plasma Membrane Transport Proteins; D017366:Serotonin Receptor Agonists; C493232:Slc6a4 protein, rat; D002065:Buspirone