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, belonging to three different classes, on high-affinity GABA(A) receptor, GABA(B) 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 GABA(A) receptor densities, defined with [H-3]gamma-aminobutyric acid ([H-3]GABA), were significantly increased following bulbectomy. This effect on B-max values was reversed by all three antidepressant drugs. GABA(B) receptor densities decreased slightly after bulbectomy. Chronic antidepressant administration had no effect on GABA(B) receptor binding parameters. Olfactory bulbectomy did not induce any changes in cortical beta-adrenoceptor binding parameters determined with [H-3]CGP-12177 ((-)-4-(3-t-butylamino-2-hydroxypropoxy)- [5,7-H-3]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 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 therapeutic effects of antidepressant treatments.