ANTIDEPRESSANT-INDUCED MODULATION OF GABA(A) RECEPTORS AND BETA-ADRENOCEPTORS BUT NOT GABA(B) RECEPTORS IN THE FRONTAL-CORTEX OF OLFACTORY BULBECTOMISED RATS

The effects of prolonged administration of antidepressant drugs, belon ging to three different classes, on high-affinity GABA(A) receptor, GA BA(B) receptor and beta-adrenoceptor binding parameters were determine d in the frontal cortex of olfactory bulbectomised rats. Clorgyline (1 mg/kg/day), paroxetine (10 mg/kg/day) or desipramine (10 mg/kg/day) w ere administered for 21 days via subcutaneous osmotic minipumps implan ted in the scapular region 7 days after bulbectomy. Cortical GABA(A) r eceptor densities, defined with [H-3]gamma-aminobutyric acid ([H-3]GAB A), were significantly increased following bulbectomy. This effect on B-max values was reversed by all three antidepressant drugs. GABA(B) r eceptor densities decreased slightly after bulbectomy. Chronic antidep ressant administration had no effect on GABA(B) receptor binding param eters. Olfactory bulbectomy did not induce any changes in cortical bet a-adrenoceptor binding parameters determined with [H-3]CGP-12177 ((-)- 4-(3-t-butylamino-2-hydroxypropoxy)- [5,7-H-3]benzimidazol-2-one). How ever, prolonged administration of all three antidepressant drugs induc ed a downregulation of beta-adrenoceptors. The results of the present study confirm the involvement of cortical GABA(A) rather than GABA(B) receptors in the olfactory bulbectomy animal model of human depression . Moreover, the data further support the hypothesis that a decrease in function of the GABA(A) receptor complex could play a role in the the rapeutic effects of antidepressant treatments.