Antidepressant-induced modulation of GABAA receptors and beta-adrenoceptors but not GABAB receptors in the frontal cortex of olfactory bulbectomised rats.
The effects of prolonged administration of antidepressant drugs, belonging to three different classes, on high-affinity GABAA receptor, GABAB receptor and beta-adrenoceptor binding parameters were determined in the frontal cortex of olfactory bulbectomised rats. Clorgyline (1 mg/kg/day), paroxetine (10 mg/kg/day) or desipramine (10 mg/kg/day) were administered for 21 days via subcutaneous osmotic minipumps implanted in the scapular region 7 days after bulbectomy. Cortical GABAA receptor densities, defined with [3H]gamma-aminobutyric acid ([3H]GABA), were significantly increased following bulbectomy. This effect on Bmax values was reversed by all three antidepressant drugs. GABAB receptor densities decreased slightly after bulbectomy. Chronic antidepressant administration had no effect on GABAB receptor binding parameters. Olfactory bulbectomy did not induce any changes in cortical beta-adrenoceptor binding parameters determined with [3H]CGP-12177 ((-)-4-(3-t- butylamino-2-hydroxypropxy)- [5,7-3H]benzimidazol-2-one). However, prolonged administration of all three antidepressant drugs induced a downregulation of beta-adrenoceptors. The results of the present study confirm the involvement of cortical GABAA rather than GABAB receptors in the olfactory bulbectomy animal model of human depression. Moreover, the data further support the hypothesis that a decrease in function of the GABAA receptor complex could play a role in the therapeutic effects of antidepressant treatments.
Dennis
T
T
McGill University, Department of Psychiatry, Montréal, Québec, Canada.
Beauchemin
V
V
Lavoie
N
N
D000319:Adrenergic beta-Antagonists / Q000008:administration & dosage / Q000494:pharmacology; D000704:Analysis of Variance; D000818:Animals; D000928:Antidepressive Agents / Q000008:administration & dosage / Q000378:metabolism / Q000494:pharmacology*; D001665:Binding Sites; D003010:Clorgyline / Q000008:administration & dosage / Q000494:pharmacology; D003891:Desipramine / Q000008:administration & dosage / Q000494:pharmacology; D015536:Down-Regulation / Q000187:drug effects; D005625:Frontal Lobe / Q000187:drug effects* / Q000378:metabolism; D015918:Infusion Pumps, Implantable; D008297:Male; D009830:Olfactory Bulb / Q000601:surgery; D017374:Paroxetine / Q000008:administration & dosage / Q000494:pharmacology; D011412:Propanolamines / Q000378:metabolism; D011506:Proteins / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D011943:Receptors, Adrenergic, beta / Q000187:drug effects* / Q000378:metabolism; D011963:Receptors, GABA-A / Q000187:drug effects* / Q000378:metabolism; D018080:Receptors, GABA-B / Q000187:drug effects* / Q000378:metabolism
D000319:Adrenergic beta-Antagonists; D000928:Antidepressive Agents; D011412:Propanolamines; D011506:Proteins; D011943:Receptors, Adrenergic, beta; D011963:Receptors, GABA-A; D018080:Receptors, GABA-B; D017374:Paroxetine; D003010:Clorgyline; C033394:CGP 12177; D003891:Desipramine